in order to overcome the drawbacks of the prior art , the goal of the present invention is to offer a process for the preparation of r - beta - amino - phenylbutyric acid derivatives of formula ( i ): ar is unsubstituted phenyl or phenyl substituted with one to five substituents selected from the group consisting of fluorine , methyl , trifluoromethyl and trifluoromethoxy . r 1 is hydrogen or c 1 - 6 alkyl . r 2 is hydrogen or an amino - protecting group , such as alkoxycarbonyl and acyl groups , wherein the alkoxycarbonyl is selected from the group consisting of methoxycarbonyl , ethoxycarbonyl and tert - butoxyl carbonyl , and the acyl is selected from the group consisting of formyl , acetyl , chloroacetyl , trichloroacetyl , benzoyl and phenyl acetyl group . the method comprises the following steps of : ( 1 ) reacting ammonium formate with unsubstituted or substituted phenyl ethyl acetoacetate to obtain an imine , and then reacting the imine with a reducing agent to obtain a racemate of beta - amino - phenylbutyric acid ester ; ( 2 ) reacting the racemate of beta - amino - phenylbutyric acid ester and a resolving agent to form a salt of r - form in an alcoholic solvent or an alcohol aqueous solution , and crystallizing the salt ; and ( 3 ) hydrolyzing the salt of r - form formed from the beta - amino - phenylbutyric acid ester and the resolving agent , or protecting the amino group of the beta - amino - phenylbutyric acid ester to obtain r - beta - amino - phenylbutyric acid derivative of formula ( i ). one embodiment of the present disclosure further comprises that r - beta - amino - phenylbutyric acid derivatives of formula ( i ) obtained in the step ( 3 ) is reacted with hydrochloride acid to obtain a hydrochloric acid salt . the chiral pharmaceutical intermediates , r - beta - amino - phenylbutyric acid derivatives of formula ( i ) disclosed in the present invention may be prepared as outlined in the following scheme : preferably , in the first product ( ia ): ar is 2 , 4 , 5 - trifluorophenyl , r 1 and r 2 are hydrogen . preferably , in the second product ( ib ): ar is 2 , 4 , 5 - trifluorophenyl , r 1 is ethyl , and r 2 is hydrogen . preferably , in the third product ( ic ): ar is 2 , 4 , 5 - trifluorophenyl , r 1 is hydrogen , and r 2 is tert - butoxyl carbonyl . in order to better illustrate the essence of the invention , taking a representative process of the preparation of chiral pharmaceutical intermediates , preferably r - beta - amino - 2 , 4 , 5 - trifluorophenylbutyric acid or pharmaceutically acceptable salts thereof as examples , the present invention is gradually set forth . a process for the preparation of r - beta - amino - 2 , 4 , 5 - trifluorophenylbutyric acid comprises the following steps . first , ammonium formate is reacted with a starting material , 2 , 4 , 5 - trifluorophenyl ethyl acetoacetate to obtain an imine . then , the imine is reduced by sodium cyanoborohydride to obtain a racemate of beta - amino - phenylbutyric acid ester . second , r - beta - amino - phenylbutyric acid ester and a resolving agent form a salt of r - form in an alcoholic solvent or an alcohol aqueous solvent . the salt of r - beta - amino - phenylbutyric acid ester is crystallized . third , the salt is hydrolyzed , or protected the amine group to obtain r - beta - amino - phenylbutyric acid derivatives of formula ( i ) or pharmaceutically acceptable salts thereof . in one embodiment of the present invention , the reducing agent used in the step ( 1 ) is sodium cyanoborohydride . the chiral resolving agent used in the step ( 2 ) is a chiral diacylated tartaric acid comprising : dibenzoyl - d - tartaric acid , dibenzoyl - l - tartaric acid , di - p - toluoyl - d - tartaric acid or di - p - toluoyl - l - tartaric acid . preferably , the chiral resolving agent is di - p - toluoyl - d - tartaric acid or di - p - toluoyl - l - tartaric acid . the resolving agent , di - p - toluoyl - l - tartaric acid or di - p - toluoyl - d - tartaric acid used in the process of the present invention can be used alone or jointly . furthermore , in the process of the preparation of r - beta - amino - phenylbutyric acid derivatives , the alcoholic solvent used in the step ( 2 ) is a lower fatty alcohol with three or less carbon atoms . preferably , it is methanol . in one embodiment of the present invention , the alcoholic aqueous solution used in the step ( 2 ) is an aqueous solution of a lower fatty alcohol with less three carbon atoms . in summary , the problem to be solved by the present invention is to prepare single enantiomers of formula ( i ) by a chemical synthesis . the process comprises resolving the racemate of beta - amino - phenylbutyric acid derivatives with a resolving agent . in the reaction scheme mentioned above , compound ( ii ), ( r 1 is c 1 - 6 alkyl or hydrogen ) can be prepared according to u . s . pat . no . 5 , 296 , 482 . 2 , 4 , 5 - trifluoro bromobenzene used as a starting material is alkylated by diethyl malonate . then , the alkylated product is hydrolyzed and decarboxylated to obtain 2 , 4 , 5 - trifluoroacetic acid . the acid is condensed with meldrum &# 39 ; s acid . then , the condensation product is alcoholyzed and decarboxylated by heating the reaction mixture to obtain 2 , 4 , 5 - trifluorophenyl ethyl acetoacetate , which can be used as the starting material for the preparation of the product of formula ( i ). 2 , 4 , 5 - trifluorophenyl acetyl acetoacetate ( ii ) ( r 1 is ethyl ) is reacted with ammonium formate to obtain an imine . then , the imine is reduced by sodium cyanoborohydride to obtain the compound ( iii ) ( r 1 is ethyl ). the compound ( iii ) is resolved with a resolving agent to obtain the compound ( iv ) ( r 1 is ethyl ). then , the compound ( iv ) is hydrolyzed , or the amine group of the compound ( iv ) is protected to obtain the product ( i ). when r 1 and r 2 are different groups as shown in the above scheme , the product ( i ) containing different substituents can represent the specific compound in the various steps , such as ( ia ), ( ib ) and ( ic ) illustrated as above . after an extensive study , the inventors have found that various commonly used acidic resolving agents are substantially ineffective for the resolution of the racemate of formula ( iii ) in the above resolving process , except that r - camphor sulfonic acid has certain selectivity . some acidic resolving agents cannot react with the racemate of formula ( iii ) to form crystalline precipitates in solvents effectively . some acidic resolving agents can react with the racemate of formula ( iii ) to form crystalline precipitates in solvents , but there is no selectivity and the resulting precipitates are still a racemic mixture . after doing some research , the inventors have identified that the ineffective resolving agents include l - tartaric acid , r - mandelic acid , n - acetyl - l - glutamic acid , l - leucine and the like . further , the inventors have found that , among a large number of conventional acidic resolving agents tested , only tartaric acids diacylated by benzoyl or substituted benzoyl , such as dibenzoyl - l - tartaric acid ( l - dbta ), dibenzoyl - d - tartaric acid ( d - dbta ), di - p - toluoyl - l - tartaric acid ( l - dtta ) or di - p - toluoyl - d - tartaric acid ( d - dtta ), can resolve the ( r ) configuration and ( s ) configuration of beta - amino - phenylbutyric acid derivatives effectively . generally , the present invention relates to a process for the preparation of r - beta - amino - phenylbutyric acid derivatives ( i ). the process not only comprises the step of the chemical preparation of a racemate of formula ( iii ), but also comprises the step of reacting a resolving agent with the racemate of formula ( iii ) to obtain the corresponding salt in an alcoholic solvent or an alcohol aqueous solution , and crystallizing the corresponding salt to obtain r - beta - amino - phenylbutyric acid derivatives of formula ( i ) or corresponding s - beta - amino - phenylbutyric acid derivatives . the resolving agent is dibenzoyl - l - tartaric acid ( l - dbta ), dibenzoyl - d - tartaric acid ( d - dbta ), di - p - toluoyl - l - tartaric acid ( l - dtta ) or di - p - toluoyl - d - tartaric acid ( d - dtta ), and preferably di - p - toluoyl - l - tartaric acid or di - p - toluoyl - d - tartaric acid . in order to obtain single enantiomers of the compounds of formula ( i ), such as r - configuration of ( ib ), 1 mol of d - dtta is reacted with 2 mol of the racemate of formula ( iii ) ( r 1 = ethyl ) in methanol to obtain the corresponding salt . the corresponding salt is crystallized to obtain the crystals with r - configuration ( iv ) ( r 1 = ethyl ). the r - configuration of compound ( ib ) is obtained from crystals . on the contrary , when l - dtta is used as a resolving agent , s - configuration product is obtained . further , the resolving process of the present invention includes a re - crystallizing step after the steps of forming and crystallizing the salt . the resolving agent , di - p - toluoyl - l - tartaric acid ( l - dtta ) and di - p - toluoyl - d - tartaric acid ( d - dtta ) used in the present invention , may be used alone or jointly . specifically , the present invention relates to a process for preparing and resolving of the intermediates , beta - amino - phenylbutyric acid derivatives of formula ( i ). the problem to be solved by the present invention is to obtain the above pharmaceutically acceptable optical pure compound of formula ( i ) of r - configuration with a good yield by using di - p - toluoyl - l - tartaric acid . the method is characterized in that the racemate of formula ( iii ) is reacted with an acidic resolving agent in a particular solvent to obtain the corresponding salt and selectively precipitate the crystals of the salts of the desired chiral intermediate , beta - amino - phenylbutyric acid derivatives . the method of resolving the intermediate amine of formula ( iii ) includes the process of reacting the intermediate amine of formula ( iii ) with a chiral resolving agent to obtain the corresponding salt , re - crystallizing the corresponding salt to form crystal precipitates and extracting the re - crystallized precipitates to obtain the intermediate amine of formula ( ib ). the resolving method can further comprise the step of hydrolyzing ( ib ) to obtain ( ia ) or protecting the amine group to obtain ( ic ). all of the chiral pharmaceutical intermediates can be used for the synthesis of a variety of active pharmaceutical compounds . with regard to the amount of the resolving agent , in theory , because an acid - base neutralization reaction needs equal numbers of moles of acid and base , the molar ratio of the amines to the resolving agent can be 2 : 1 . if the salt with the certain configuration is desired , the molar ratio can be 4 : 1 . if acid addition salts with equal molar amounts of acid and base are desired , the molar ratio can be 1 : 1 . however , after doing some research , the inventors found that a higher proportion of the resolving agent gives more satisfactory yields of a resolving product with high chiral purity . generally speaking , the suitable molar ratio of amine intermediates to the resolving agent can be from 4 : 1 to 1 : 1 , the preferable molar ratio is 2 : 1 to 1 : 1 . excessive amount of the resolving agent does not improve the resolution . the resolving process of a racemate of formula ( iii ) can be carried out in a conventional solvent . preferably , the process is in an organic solvent , more preferably in an alcoholic solvent . the alcoholic solvent could be used alone or in combination with other organic solvents . alcoholic solvents used in the present invention include alcoholic solvents used alone as well as alcohol - base mixed solvents . the alcoholic solvent can be a lower fatty alcohol with three or less carbon atoms . preferably , the solvent is methanol . the alcoholic aqueous solution can be aqueous solution of a short - chain alcohol mentioned above . in order to improve the chiral purity of the amines of formula ( i ), sometimes it is necessary to recrystallize the resolving salt obtained . the resolving process can generally be carried out at room temperature ; if necessary , under heating conditions . generally , the re - crystallizing step is carried out under heating condition . first , the salt obtained from the resolution is dissolved in a particular solvent and then re - crystallization is completed slowly at room temperature . in general , after re - crystallizing twice , the chiral purity is often satisfactory , and the ee value is generally above 99 %. the process to obtain the free intermediate is conventional wherein the base used is preferably sodium bicarbonate . the extracting solvent can be a hydrophobic organic solvent used in conventional extractions , such as ethyl acetate , methylene chloride and chloroform , etc ., preferably ethyl acetate and chloroform . the process of hydrolyzing the compound of formula ( i ) is also conventional , and the base used is preferably sodium hydroxide . the acid used in the salt formation is preferably hydrochloride acid . the salt formation method is conventional . it can be readily performed by a person with ordinary skill in the art . the optical purity of the ester or acid of the compound formula ( i ) according the present invention is more than 99 %, particularly suitable as a synthetic intermediate of chiral drugs . the present invention is illustrated by the following examples in detail , which should not be construed as limiting the scope of the present invention . 114 g ( 0 . 60 mol ) of 2 , 4 , 5 - trifluorophenylacetic acid was dissolved in 600 ml of thf . to this mixture , 107 g ( 0 . 66 mol ) of carbonyldiimidazole was added with stirring ( when a part of carbonyldiimidazole was added , a lot of solid was formed ; subsequently , the solid thereby dissolved in the solution with further addition ). upon completion of the addition , the reaction mixture was warmed to 50 ° c . 95 . 1 g ( 0 . 66 mol ) of meldrum &# 39 ; s acid was added , and the mixture was aged for 3 hours at 50 ° c . the mixture was concentrated to remove thf and the residue was dissolved in water ( 600 ml ) and dichloromethane ( 800 ml ), and then the ph value was adjusted to 2 . the aqueous phase was separated and the organic phase was washed with 0 . 1n hcl and water ( 600 ml ) respectively . the organic phase was dried and concentrated to obtain 182 g of a condensate , 5 -[ 2 -( 2 , 4 , 5 - trifluorophenyl )- acetyl ]- 2 , 2 - dimethyl - 1 , 3 - dioxane - 4 , 6 - dione , as a solid ( the re - crystallization can be carried out in ethyl acetate to obtain a white solid ). melting point : 101 . 5 - 103 . 5 ° c ., yield : 96 %. 60 g of the condensate ( 0 . 190 mol ) obtained from the preparation example 1 was dissolved in ethanol ( 600 ml ). the mixture was stirred at 70 ° c . for 3 hours , and a solution of 2 , 4 , 5 - trifluorophenyl ethyl acetoacetate in ethanol was obtained . 70 g of formic acid ( 1 . 11 mol ) was added to the mixture , and the reaction mixture was heated to reflux for 3 hours . after cooling to 40 ° c ., 15 g of sodium cyanoborohydride ( 0 . 239 mol ) was added slowly to the reaction mixture , and the reaction mixture was heated to reflux for 2 hours . after cooling , the mixture was concentrated to remove ethanol and the residue was dissolved in water , the ph value was adjusted to 9 . the mixture was extracted with dichloromethane and washed with a small amount of water . the organic phase was dried and concentrated to obtain 45 g of beta - amino - phenylbutyric acid ethyl ester as a brown oil . yield : 90 . 5 %. 5 . 18 g ( 20 mmol ) of the racemate of beta - amino - phenylbutyric acid ethyl ester was dissolved in methanol ( 60 ml ), and 3 . 86 g ( 10 mmol ) of d - dtta was added with stirring . a lot of white solid precipitated quickly from the reaction solution . the mixture was heated to reflux for 1 - 2 hours ( the solid was not completely dissolved in the solution ). after cooling to below 10 ° c ., the resulting precipitates were collected by filtration and washed with a small amount of methanol , and then the re - crystallization was carried out in methanol . after re - crystallizing twice , 3 . 37 g of a white powder was obtained . melting point : 187 . 0 - 188 . 0 ° c ., [ a ] d 25 =+ 96 . 7 ° ( c1 , 0 . 1 m naoh ). 3 . 0 g of the white solid was treated with a base to obtain 1 . 20 g of r - beta - amino - phenylbutyric acid ethyl ester ( ib ). the optical purity of ( ib ) was more than 99 . 7 %, and the first resolving yield was 52 . 2 %. the resulting residual solutions during the above resolving process and the twice re - crystallization processes were combined and then concentrated to dryness to obtain a crude product . the crude product was treated with saturated sodium bicarbonate to obtain the free amine . the solution was extracted with chloroform to obtain 4 . 7 g of a racemate mainly composed of s - configuration . hplc analysis showed 71 . 3 % of s - configuration . the racemate was dissolved in methanol ( 60 ml ), and 3 . 86 g of l - dtta ( 10 mmol ) was added for inverse resolution . the mixture was heated to reflux until a clear solution was obtained . after cooling , crystals precipitated from the reaction solution . the resulting precipitates were collected by filtration and then were dried to obtain a crude product . hplc analysis showed 95 . 6 % of s - configuration . the crude product of s - configuration was dissolved in 60 ml of methanol , and the mixture was heated to reflux until a clear solution was obtained . after cooling , crystals precipitated from the solution . the resulting precipitates were collected by filtration and then dried to obtain 3 . 44 g of a salt of l - dtta of s - configuration . melting point : 182 . 0 - 183 . 5 ° c ., [ a ] d 25 =− 90 . 3 ° ( c1 , 0 . 1 m naoh ). the reverse resolving yield was 53 . 3 %. hplc analysis showed 98 . 4 % of s - configuration . the residual solution during the above reverse resolving process and re - crystallization process was combined , and then concentrated to dryness to obtain a crude product . the crude product was treated with saturated sodium bicarbonate to obtain the free amine . the solution was extracted with chloroform to obtain 1 . 9 g of a racemate composed of mainly of r - configuration . hplc analysis showed 67 . 4 % of r - configuration . the racemate was dissolved in 20 ml of methanol , and 1 . 5 g of d - dtta was added . the mixture was heated to reflux until a clear solution was obtained . after cooling , crystals precipitated from the resolution . the precipitate was collected by filtration and dried to obtain 0 . 92 g of a salt . hplc analysis showed 99 . 30 % of r - configuration . the resulting salt was treated with saturated sodium bicarbonate to obtain the free amine . the solution was extracted with chloroform to obtain 0 . 5 g of the intermediate amine ( ib ) of r - configuration . yield : 19 . 5 %. hplc analysis showed 99 . 3 % of r - configuration . the total resolving yield was 71 . 4 %. 5 . 18 g ( 20 mmol ) of the racemate of beta - amino - phenylbutyric acid ethyl ester was dissolved in methanol ( 60 ml ), and 3 . 86 g ( 10 mmol ) of l - dtta was added with stirring . a lot of white solid precipitated quickly from the reaction solution . the mixture was heated to reflux for 1 - 2 hours ( the solid was not completely dissolved in the solution ). after cooling to below 10 ° c ., the resulting precipitates were collected by filtration and washed with a small amount of methanol . the residual solution was concentrated to dryness and 70 ml of water was added , the ph value was adjusted to 8 with a saturated sodium bicarbonate solution . the mixture was extracted with dichloromethane . the organic phase was washed with water and concentrated to obtain an oil product . the oil product was dissolved in methanol ( 60 ml ), and 3 . 86 g of d - dtta ( 10 mmol ) was added with stirring . a lot of white solid precipitated quickly from the reaction solution . the mixture was heated to reflux for 1 - 2 hours ( the solid was not completely dissolved in the solution ). after cooling to below 10 ° c ., crystals precipitated from the solution . the resulting precipitates was collected by filtration and washed with a small amount of methanol , and then the re - crystallization was carried out in methanol . after re - crystallization , 4 . 17 g of a white powder was obtained . melting point : 185 . 0 - 186 . 5 ° c ., [ a ] d 25 =+ 95 . 8 ° ( c1 , 0 . 1 m naoh ). 4 . 0 g of the white solid was treated with a base to obtain 1 . 61 g of r - beta - amino - phenylbutyric acid ethyl ester ( ib ). the optical purity of ib was more than 99 . 7 % and the resolving yield was 64 . 8 %. 5 . 18 g ( 20 mmol ) of the racemate of beta - amino - phenylbutyric acid ethyl ester was dissolved in ethanol ( 120 ml ), and 3 . 86 g of d - dtta ( 10 mmol ) was added with stirring . the mixture was heated to reflux until a clear solution was obtained . after cooling , crystals precipitated from the solution . the resulting precipitates were collected by filtration and dried to obtain the crude product . hplc analysis showed 89 . 4 % of r - configuration . the re - crystallization of the crude product carried out in ethanol ( 120 ml ). after re - crystallization twice , 2 . 82 g of a white solid was obtained . melting point : 186 . 0 - 187 . 0 ° c ., [ a ] d 25 =+ 96 . 4 ° ( c1 , 0 . 1 m naoh ). hplc analysis showed 99 . 1 % of r - configuration . the white solid was dissolved in 20 ml of water , and the ph value was adjusted to 8 - 9 with anhydrous sodium carbonate . the mixture was extracted with dichloromethane twice ( 10 ml × 2 ). the organic phase was combined and washed with water , the organic phase was concentrated to dryness to obtain 1 . 13 g of r - beta - amino - 2 , 4 , 5 - trifluorophenylbutyric acid ethyl ester ( ib ). [ a ] d 25 =− 2 . 6 ° ( c = 0 . 8 , methanol ). the resolving yield was 43 . 6 %. 5 . 18 g ( 20 mmol ) of the racemate of beta - amino - phenylbutyric acid ethyl ester was dissolved in ethanol ( 100 ml ), and 3 . 58 g of d - dbta ( 10 mmol ) was added with stirring . the mixture was heated to reflux until a clear solution was obtained . after cooling , crystals precipitated from the solution . the resulting precipitates were collected by filtration and dried to obtain the crude product . hplc analysis showed 83 . 37 % of r - configuration . the re - crystallization of the crude product carried out in ethanol ( 100 ml ). after re - crystallization twice , 2 . 59 g of a white solid was obtained . hplc analysis showed 99 . 2 % of r - configuration . the white solid was dissolved in 18 ml of water , and the ph value was adjusted to 8 - 9 by anhydrous sodium carbonate . the mixture was extracted with dichloromethane twice ( 10 ml × 2 ). the organic phase was combined and washed with water , the organic phase was concentrated to dryness to obtain 1 . 03 g of r - beta - amino - 2 , 4 , 5 - trifluorophenylbutyric acid ethyl ester ( ib ). [ a ] d 25 =− 2 . 7 ° ( c = 0 . 8 , methanol ). the resolving yield was 39 . 8 %. 1 g ( 3 . 84 mmol ) of r - beta - amino - 2 , 4 , 5 - trifluorophenylbutyric acid ethyl ester ( ib ) was added to the mixture of methanol ( 10 ml ) and sodium carbonate aqueous solution ( 10 ml ), in which the ph value was 10 , and then 1 . 0 g of ( boc ) 2 o was added . the reaction mixture was reacted at 30 ° c . for 3 hours . after the reaction was completed , 4 m naoh ( 8 ml ) was added to the mixture . the hydrolyzation was carried out at 40 - 45 ° c . after 2 hours , the reaction was detected by tlc . the solvent was evaporated , and the ph was slowly adjusted to 3 . the mixture was extracted with ethyl acetate and washed with acidic water . the organic phrase was dried and concentrated , and then crystals precipitated to obtain 1 . 14 g of r - beta - t - butoxyl carbonyl amino - 2 , 4 , 5 - trifluorophenylbutyric acid ( ic ). melting point : 127 - 128 ° c . [ a ] d 25 = 14 . 2 ° ( c = 1 , methanol ). yield : 89 . 1 %. 1 . 0 g ( 3 . 0 mmol ) of r - beta - t - butoxyl carbonyl amino - 2 , 4 , 5 - trifluorophenylbutyric acid ( ic ) was added to 20 ml of the mixture of ethyl acetate and hcl ( 2 m ). the mixture was stirred for 4 hours at room temperature . the solution was concentrated to half its volume at low temperature , and crystals precipitated from the solution . the resulting precipitates were collected by filtration and dried to obtain 0 . 67 g of r - beta - amino - 2 , 4 , 5 - trifluorophenylbutyric acid hydrochloride salt ( ia ). melting point : 204 . 5 - 207 . 5 ° c . [ a ] d 25 =− 6 . 8 ° ( c = 0 . 8 , methanol ). yield : 82 . 8 %. 1 . 0 g of r - beta - amino - 2 , 4 , 5 - trifluorophenylbutyric acid ethyl ester ( ib ) ( 3 . 84 mmol ) was dissolved in 10 ml of methanol , and 4 m sodium hydroxide ( 6 ml ) was added . the hydrolyzation was carried out at 40 ° c . after 2 hours , the reaction was detected by tlc . the ph value was adjusted to 3 , and the solvent was concentrated to dryness . the residue was dissolved in chloroform and methanol ( 4 : 1 ). the undissolved compounds were removed by filtration , and the filtrate was placed on a silica gel column . the main fraction was collected and concentrated to dryness . 16 ml of ethyl acetate was added to the residue and the mixture was stirred for 2 hours at room temperature . crystals precipitated from the solution and dried to obtain 0 . 90 g of r - beta - amino - 2 , 4 , 5 - trifluorophenylbutyric acid hydrochloride salt ( ia ). melting point : 203 . 0 - 206 . 0 ° c . [ a ] d 25 =− 6 . 4 ° ( c = 0 . 8 , methanol ). yield : 87 . 1 %.