CN116063210B - Method for chiral synthesis of D-p-methylsulfonyl phenylserine ethyl ester - Google Patents
Method for chiral synthesis of D-p-methylsulfonyl phenylserine ethyl ester Download PDFInfo
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Abstract
The invention discloses a method for chiral synthesis of D-p-methylsulfonyl phenylserine ethyl ester, which is characterized by comprising the following steps: preparing an intermediate product and reducing to remove phenylethane; the intermediate (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate is added into ethanol, then Pd/C catalyst is added, the temperature is raised to 90-105 ℃ in the hydrogen atmosphere of 3.0-6.0MPa, after reaction for 1-1.5h at 90-105 ℃, the mixture is cooled, filtered, distilled under reduced pressure, rinsed and dried, and D-p-methylsulfonyl phenylserine ethyl ester is obtained; the D-p-methylsulfonyl phenylserine ethyl ester synthesized by the method has high purity and yield, can avoid generating a large amount of wastewater, and can not generate extremely toxic waste gas such as hydrogen sulfide.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for chiral synthesis of D-p-methylsulfonyl phenylserine ethyl ester.
Background
The antibacterial drug for animals, developed in the 20 th century 70, has an antibacterial spectrum and an antibacterial activity slightly superior to those of thiamphenicol, and has stronger antibacterial activity on various gram-positive bacteria, gram-negative bacteria, mycoplasma and the like. The haemolytic Pasteurella multocida and the Pasteurella multocida are highly sensitive to the product, and the streptococcus, shigella dysenteriae, salmonella typhi, klebsiella, escherichia coli and haemophilus are sensitive to the product. D-p-methylsulfonyl phenylserine ethyl ester (D-ethyl ester for short) is a key intermediate of florfenicol, and the currently mainstream D-ethyl ester synthesis method is that p-methylsulfonyl benzaldehyde, glycine and copper sulfate react to generate copper salt, the copper salt and ethanol are used for generating D, L-ethyl ester under the catalysis of concentrated sulfuric acid, the D, L-ethyl ester is resolved by tartaric acid to obtain the D-ethyl ester, and the L-ethyl ester is racemized and used. The overall yield of the process is very low (40% -50% according to the report of the literature), a large amount of wastewater is generated, and hydrogen sulfide waste gas is generated in the copper removal process.
Chinese patent CN103936638B discloses a new chiral synthesis method of florfenicol, which is composed of a series of reactions such as cyclization, selective reduction, fluorinated ring opening, deprotection, acylation reaction, hydroxysulfonation configuration conversion reaction, hydrolysis reaction, etc., but the materials such as aluminum chloride and bromine are used in the patent, a large amount of byproducts are generated, and the treatment is difficult.
Chinese patent CN106187837B discloses a biosynthesis method, in which (S) -hydroxycyano lyase is used to perform catalytic addition reaction in the first step, and then substitution, addition, reduction and acylation reaction are performed to synthesize florfenicol, but the (S) -hydroxycyano lyase used in the patent is very unstable, and meanwhile, the reaction process is difficult to control due to the use of grignard reagent, and the amount of waste liquid after treatment is very large.
Chinese patent CN106349130B discloses a method for asymmetric synthesis of florfenicol, in which a henry reaction is performed in a catalyst, and then florfenicol is synthesized by a reduction reaction and an acylation reaction, but fluoronitroethane used in the patent is dangerous and explodes during use.
Chinese patents CN106748920B and CN110642765A disclose conventional methods for preparing D, L-ethyl ester (florfenicol intermediate), which are first condensation reactions, and esterification reactions are performed, but the wastewater treatment amount of the method is large, and simultaneously highly toxic gases such as hydrogen sulfide are generated in the copper removal process.
At DOI:10.1016/j. Tetasy.2011.07.011 Tetrahedron: asymmetryVolume 22,Issue12,30 June 2011,Pages:1337-1341 (Received 30 May2011,Accepted 6 July 2011,Available online 16 August 2011) discloses the synthesis of florfenicol by an asymmetric method, most of the reagents used in this document are not commercially available or are very expensive and are not suitable for industrial production.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention provides a chiral method for synthesizing D-p-methylsulfonylphenyl serine ethyl ester, which adopts alpha-phenethylamine and ethyl chloroacetate to react and then react with p-methylsulfonylbenzaldehyde, the D-p-methylsulfonylbenzene serine ethyl ester is synthesized after phenylethane is reduced and removed, the purity and the yield of the synthesized D-p-methylsulfonylbenzene serine ethyl ester are high, a large amount of wastewater can be avoided, and extremely toxic waste gases such as hydrogen sulfide and the like can not be generated.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a chiral synthesis method of D-p-methylsulfonyl phenylserine ethyl ester comprises the following synthetic route:
A method for chiral synthesis of D-p-methylsulfonylbenzenesulfonyl ethyl ester comprises the following steps: preparing an intermediate product and reducing to remove phenylethane;
adding alpha-phenethylamine and ethyl chloroacetate into ethanol, stirring, then dripping ethanolamine, controlling the dripping time to be 1-2h, preserving heat at 30-35 ℃ for 1.5-2h after dripping, then adding p-methylsulfonyl benzaldehyde, heating to 50-65 ℃, preserving heat for 5-6.5h, cooling to 5-10 ℃, separating and drying to obtain an intermediate (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
in the preparation of the intermediate product, the stirring speed during stirring is 200-300rpm;
in the preparation intermediate product, the weight ratio of ethanol to alpha-phenethylamine to ethyl chloroacetate to ethanolamine to p-methylsulfonyl benzaldehyde is 150:33.33-37.5:34.72-39.82:20.1-22.32:47.12-54.72;
the intermediate (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate is added into ethanol, then Pd/C catalyst is added, the temperature is raised to 90-105 ℃ in the hydrogen atmosphere of 3.0-6.0MPa, after reaction for 1-1.5h at 90-105 ℃, the mixture is cooled, filtered, distilled under reduced pressure, rinsed and dried, and D-p-methylsulfonyl phenylserine ethyl ester is obtained;
in the reduction de-phenylethane, the weight ratio of the intermediate product (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate to ethanol to Pd/C catalyst is 79.70-87.76:415.83-515.57:0.88-1.25;
in the reduction phenylethane, the Pd/C catalyst has a palladium content of 10%.
Compared with the prior art, the invention has the beneficial effects that:
(1) According to the method for chiral synthesis of D-p-methylsulfonyl phenylserine ethyl ester, chiral amine and ethyl chloroacetate are used for reaction and then directly react with p-aldehyde, and the D-p-methylsulfonyl phenylserine ethyl ester is directly synthesized due to the effect of steric hindrance, so that hazardous waste can be obviously shortened and reduced, a large amount of waste water is avoided, the reaction condition is relatively mild, the industrialization difficulty is low, and the development space and the competition capability are very strong;
(2) The chiral synthesis method of D-p-methylsulfonylphenyl serine ethyl ester can improve the purity and the yield of the synthesized D-p-methylsulfonylphenyl serine ethyl ester, and the purity of the prepared D-p-methylsulfonylphenyl serine ethyl ester is 90.02-96.32%, and the yield is 64.54-69.60%.
Drawings
FIG. 1 is a liquid chromatogram of D-p-methylsulfonylbenzenesulfonic acid ethyl ester prepared in example 1;
FIG. 2 is a liquid chromatogram of D-p-methylsulfonylbenzenesulfonic acid ethyl ester prepared in example 2;
FIG. 3 is a liquid chromatogram of D-p-methylsulfonylbenzenesulfonic acid ethyl ester prepared in example 3;
FIG. 4 is a liquid chromatogram of D-p-methylsulfonylbenzenesulfonic acid ethyl ester prepared in example 4;
FIG. 5 is a liquid chromatogram of D-p-methylsulfonylbenzenesulfonic acid ethyl ester prepared in example 5;
FIG. 6 is a liquid chromatogram of D-p-methylsulfonylbenzenesulfonic acid ethyl ester prepared in example 6;
FIG. 7 is a liquid chromatogram of D-p-methylsulfonylbenzenesulfonic acid ethyl ester prepared in example 7;
FIG. 8 is a liquid chromatogram of D-p-methylsulfonylbenzenesulfonic acid ethyl ester prepared in example 8.
Detailed Description
Specific embodiments of the present invention will now be described in order to provide a clearer understanding of the technical features, objects and effects of the present invention.
The yields in the examples were calculated as the amount of p-methylsulfonylbenzaldehyde.
Example 1
Adding 37.50g of alpha-phenethylamine and 39.06g of ethyl chloroacetate into 150g of ethanol, starting stirring, controlling the stirring speed to 200rpm, then dropwise adding 22.32g of sodium ethoxide, controlling the dropwise adding time to be 1.5h, preserving heat for 1.5h at 32 ℃ after the dropwise adding is finished, adding 53.01g of p-methylsulfonyl benzaldehyde, heating to 55 ℃, preserving heat for 5h, cooling the material to 6 ℃ after the preserving heat is finished, separating and drying to obtain 87.37g of product 1, namely (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
87.37g of the product 1 is added into 480.54g of ethanol, 1.05g of Pd/C catalyst is added, hydrogen is filled to 3.5Mpa, the temperature is raised to 95 ℃ for reduction reaction, after the reaction is carried out for 1h, the reaction is finished, the Pd/C catalyst is filtered out after cooling to room temperature, the solvent, the phenylethane and the ethanol are recovered through reduced pressure distillation, D-p-methylsulfonylphenyl serine ethyl ester wet product is obtained, 200.08g of ethanol is used for rinsing the D-p-methylsulfonylphenyl serine ethyl ester wet product, drying is carried out, 57.43g of finished D-p-methylsulfonylphenyl serine ethyl ester is obtained, liquid chromatogram analysis is carried out on the prepared D-p-methylsulfonylphenyl serine ethyl ester, the obtained liquid chromatogram is shown in fig. 1, and the purity of the prepared D-p-methylsulfonylphenyl serine ethyl ester is 95.63%, and the yield is 66.42% as can be seen from fig. 1;
the Pd/C catalyst has a palladium content of 10%.
Example 2
Adding 35.71g of alpha-phenethylamine and 37.92g of ethyl chloroacetate into 150g of ethanol, starting stirring, controlling the stirring speed to 210rpm, then dropwise adding 21.86g of sodium ethoxide, controlling the dropwise adding time to be 2h, preserving heat for 1.5h at 35 ℃ after the dropwise adding is finished, adding 52.12g of p-methylsulfonyl benzaldehyde, heating to 50 ℃, preserving heat for 6h, cooling the material to 10 ℃ after the preserving heat is finished, separating and drying to obtain 87.70g of product 1, namely (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
adding 87.70g of product 1 into 438.49g of ethanol, adding 0.88g of Pd/C catalyst, filling hydrogen to 4.5Mpa, heating to 105 ℃ for reduction reaction, cooling to room temperature after reaction for 1.5h, filtering out the Pd/C catalyst, recovering solvent, phenylethane and ethanol by reduced pressure distillation to obtain a D-p-methylsulfonylphenyl serine ethyl ester wet product, rinsing the D-p-methylsulfonylphenyl serine ethyl ester wet product by using 244.68g of ethanol, drying to obtain 58.29g of finished D-p-methylsulfonylphenyl serine ethyl ester, carrying out liquid chromatography analysis on the prepared D-p-methylsulfonylphenyl serine ethyl ester, and obtaining a liquid chromatogram which is shown in fig. 2, wherein the purity of the prepared D-p-methylsulfonylphenyl serine ethyl ester is 90.02% and the yield is 64.54% as can be seen from fig. 2;
the Pd/C catalyst has a palladium content of 10%.
Example 3
Adding 34.09g of alpha-phenethylamine and 35.51g of ethyl chloroacetate into 150g of ethanol, starting stirring, controlling the stirring speed to 220rpm, then dropwise adding 20.48g of sodium ethylate, controlling the dropwise adding time to be 1h, preserving heat at 34 ℃ for 1.6h after the dropwise adding is finished, adding 49.23g of p-methylsulfonyl benzaldehyde, heating to 60 ℃, preserving heat for 5h, cooling the material to 8 ℃ after the preserving heat is finished, separating and drying to obtain 84.33g of a product 1, namely (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
84.33g of the product 1 is added into 505.99g of ethanol, 1.10g of Pd/C catalyst is added, hydrogen is filled to 5.5Mpa, the temperature is raised to 100 ℃ for reduction reaction, after the reaction is carried out for 1.2h, the reaction is finished, the Pd/C catalyst is filtered out after cooling to room temperature, the solvent, the phenylethane and the ethanol are recovered through reduced pressure distillation, D-p-methylsulfonylphenyl serine ethyl ester wet product is obtained, 203.04g of ethanol is used for rinsing and drying the D-p-methylsulfonylphenyl serine ethyl ester wet product, 55.92g of finished D-p-methylsulfonylphenyl serine ethyl ester is obtained, the prepared D-p-methylsulfonylphenyl serine ethyl ester is subjected to liquid chromatographic analysis, the liquid chromatographic chart is shown in figure 3, and the purity of the prepared D-p-methylsulfonylphenyl serine ethyl ester is 95.53% and the yield is 69.57% as can be seen from figure 3;
the Pd/C catalyst has a palladium content of 10%.
Example 4
Adding 34.09g of alpha-phenethylamine and 35.17g of ethyl chloroacetate into 150g of ethanol, starting stirring, controlling the stirring speed to 240rpm, then dropwise adding 20.1g of sodium ethoxide, controlling the dropwise adding time to be 1.6h, preserving heat for 1.5h at 35 ℃ after the dropwise adding is finished, adding 48.71g of p-methylsulfonyl benzaldehyde, heating to 62 ℃, preserving heat for 5.6h, cooling the material to 10 ℃ after the preserving heat is finished, separating and drying to obtain 79.97g of product 1, namely (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
79.97g of the product 1 is added into 415.83g of ethanol, 1.20g of Pd/C catalyst is added, hydrogen is filled to 3.0Mpa, the temperature is raised to 105 ℃ for reduction reaction, after the reaction is carried out for 1h, the reaction is finished, the Pd/C catalyst is filtered out after cooling to room temperature, the solvent, the phenylethane and the ethanol are recovered through reduced pressure distillation, D-p-methylsulfonylphenyl serine ethyl ester wet product is obtained, 225.83g of ethanol is used for rinsing the D-p-methylsulfonylphenyl serine ethyl ester wet product, 52.12g of finished D-p-methylsulfonylphenyl serine ethyl ester is obtained, liquid chromatography analysis is carried out on the prepared D-p-methylsulfonylphenyl serine ethyl ester, the obtained liquid chromatography is shown in fig. 4, and the purity of the prepared D-p-methylsulfonylphenyl serine ethyl ester is 95.60% and the yield is 65.58% as can be seen from fig. 4;
the Pd/C catalyst has a palladium content of 10%.
Example 5
Adding 36.59g of alpha-phenethylamine and 38.85g of ethyl chloroacetate into 150g of ethanol, starting stirring, controlling the stirring speed to 250rpm, then dropwise adding 22.19g of sodium ethylate, controlling the dropwise adding time to be 2h, keeping the temperature at 30 ℃ for 1.5h after the dropwise adding is finished, adding 52.83g of p-methylsulfonyl benzaldehyde, heating to 55 ℃, keeping the temperature for 6.5h, cooling the material to 5 ℃ after the heat preservation is finished, separating and drying to obtain 87.76g of product 1, namely (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
adding 87.76g of product 1 into 482.67g of ethanol, adding 0.97g of Pd/C catalyst, filling hydrogen to 4.5Mpa, heating to 90 ℃ for reduction reaction, cooling to room temperature after reaction for 1h to filter out the Pd/C catalyst, recovering solvent, phenylethane and ethanol by reduced pressure distillation to obtain a D-p-methylsulfonyl phenylserine ethyl ester wet product, rinsing the D-p-methylsulfonyl phenylserine ethyl ester wet product by using 242.74g of ethanol, drying to obtain 57.77g of finished D-p-methylsulfonyl phenylserine ethyl ester, and carrying out liquid chromatography analysis on the prepared D-p-methylsulfonyl phenylserine ethyl ester to obtain a liquid chromatogram, wherein the purity of the prepared D-p-methylsulfonyl phenylserine ethyl ester is 96.32% as can be seen from FIG. 5, and the yield is 67.53%;
the Pd/C catalyst has a palladium content of 10%.
Example 6
Adding 33.33g of alpha-phenethylamine into 150g of ethanol, adding 34.72g of ethyl chloroacetate, starting stirring, controlling the stirring speed to 260rpm, then dropwise adding 20.4g of sodium ethylate, controlling the dropwise adding time to be 1.5h, preserving heat at 35 ℃ for 2h after the dropwise adding is finished, adding 47.12g of p-methylsulfonyl benzaldehyde, heating to 60 ℃, preserving heat for 5h, cooling the material to 8 ℃ after the preserving heat is finished, separating and drying to obtain 79.70g of (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
79.70g of the product 1 is added into 454.30g of ethanol, 1.04g of Pd/C catalyst is added, hydrogen is filled to 6.0Mpa, the temperature is raised to 100 ℃ for reduction reaction, the reaction is carried out for 1.5h, after the reaction is finished, the Pd/C catalyst is filtered out after cooling to room temperature, the solvent, the phenylethane and the ethanol are recovered through reduced pressure distillation, D-p-methylsulfonylphenyl serine ethyl ester wet product is obtained, 204.64g of ethanol is used for rinsing and drying the D-p-methylsulfonylphenyl serine ethyl ester wet product, 52.34g of finished D-p-methylsulfonylphenyl serine ethyl ester is obtained, the prepared D-p-methylsulfonylphenyl serine ethyl ester is subjected to liquid chromatographic analysis, the liquid chromatographic chart is shown in figure 6, and the purity of the prepared D-p-methylsulfonylphenyl serine ethyl ester is 96.32% and the yield is 68.59% as can be seen from figure 6;
the Pd/C catalyst has a palladium content of 10%.
Example 7
Adding 34.88g of alpha-phenethylamine and 36.69g of ethyl chloroacetate into 150g of ethanol, starting stirring, controlling the stirring speed to 280rpm, then dropwise adding 21.55g of sodium ethylate, controlling the dropwise adding time to be 1h, preserving heat at 33 ℃ for 1.5h after the dropwise adding is finished, adding 50.91g of p-methylsulfonyl benzaldehyde, heating to 55 ℃, preserving heat for 5.7h, cooling the material to 7 ℃ after the preserving heat is finished, separating and drying to obtain 83.13g of product 1, namely (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
83.13g of product 1 is added into 498.76g of ethanol, 1.25g of Pd/C catalyst is added, hydrogen is filled to reach 3.5Mpa, the temperature is raised to 95 ℃ for carrying out reduction reaction, after the reaction is carried out for 1.5 hours, the reaction is completed, the Pd/C catalyst is cooled to room temperature and filtered out, the solvent is recovered under reduced pressure, phenylethane and ethanol are recovered, D-p-methylsulfonylphenyl serine ethyl ester wet product is obtained after separation, 246.05g of ethanol is used for rinsing and drying the D-p-methylsulfonylphenyl serine ethyl ester wet product, 55.12g of finished D-p-methylsulfonylphenyl serine ethyl ester is obtained, liquid chromatography analysis is carried out on the prepared D-p-methylsulfonylphenyl serine ethyl ester, the liquid chromatography is shown in fig. 7, and the purity of the prepared D-p-methylsulfonylphenyl serine ethyl ester is 96.09%, and the yield is 66.70% as can be seen from fig. 7;
the Pd/C catalyst has a palladium content of 10%.
Example 8
Adding 37.50g of alpha-phenethylamine and 39.82g of ethyl chloroacetate into 150g of ethanol, starting stirring, controlling the stirring speed to 300rpm, then dropwise adding 22.11g of sodium ethylate, controlling the dropwise adding time to be 1.6h, preserving heat for 1.5h at 35 ℃ after the dropwise adding is finished, adding 54.72g of p-methylsulfonyl benzaldehyde, heating to 65 ℃, preserving heat for 6h, cooling the material to 9 ℃ after the preserving heat is finished, separating and drying to obtain 86.43g of product 1, namely (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
86.43g of the product 1 is added into 515.57g of ethanol, 1.12g of Pd/C catalyst is added, hydrogen is filled to 5.0Mpa, the temperature is raised to 100 ℃ for reduction reaction, after the reaction is carried out for 1.2h, the reaction is finished, the Pd/C catalyst is filtered out after cooling to room temperature, the solvent, the phenylethane and the ethanol are recovered through reduced pressure distillation, D-p-methylsulfonylphenyl serine ethyl ester wet product is obtained, 302.50g of ethanol is used for rinsing and drying the D-p-methylsulfonylphenyl serine ethyl ester wet product, 62.02g of finished D-p-methylsulfonylphenyl serine ethyl ester is obtained, the prepared D-p-methylsulfonylphenyl serine ethyl ester is subjected to liquid chromatographic analysis, the liquid chromatographic chart is shown in figure 8, and the purity of the prepared D-p-methylsulfonylphenyl serine ethyl ester is 95.79% and the yield is 69.60% as can be seen from figure 8;
the Pd/C catalyst has a palladium content of 10%.
The percentages used in the present invention are mass percentages unless otherwise indicated.
Finally, it should be noted that: the foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited thereto, but it is to be understood that modifications and equivalents of some of the technical features described in the foregoing embodiments may be made by those skilled in the art, although the present invention has been described in detail with reference to the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (3)
1. A method for chiral synthesis of D-p-methylsulfonylbenzenesulfonyl ethyl ester, which is characterized by comprising the following steps: preparing an intermediate product and reducing to remove phenylethane;
adding alpha-phenethylamine and ethyl chloroacetate into ethanol, stirring, then dripping ethanolamine, controlling the dripping time to be 1-2h, preserving heat at 30-35 ℃ for 1.5-2h after dripping, then adding p-methylsulfonyl benzaldehyde, heating to 50-65 ℃, preserving heat for 5-6.5h, cooling to 5-10 ℃, separating and drying to obtain an intermediate (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate;
in the preparation intermediate product, the weight ratio of ethanol to alpha-phenethylamine to ethyl chloroacetate to ethanolamine to p-methylsulfonyl benzaldehyde is 150:33.33-37.5:34.72-39.82:20.1-22.32:47.12-54.72;
the intermediate (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate is added into ethanol, then Pd/C catalyst is added, the temperature is raised to 90-105 ℃ in the hydrogen atmosphere of 3.0-6.0MPa, after reaction for 1-1.5h at 90-105 ℃, the mixture is cooled, filtered, distilled under reduced pressure, rinsed and dried, and D-p-methylsulfonyl phenylserine ethyl ester is obtained;
in the reduction de-phenylethane, the weight ratio of the intermediate product (2S, 3R) -3-hydroxy-3- [4- (methylsulfonyl) phenyl ] -2- [ (1-phenylethyl) amino ] ethyl propionate to ethanol to Pd/C catalyst is 79.70-87.76:415.83-515.57:0.88-1.25.
2. The method for chiral synthesis of D-p-methylsulfonylbenzenesser ethyl ester according to claim 1, wherein the stirring rotation speed during stirring in the preparation of the intermediate product is 200-300rpm.
3. The method for chiral synthesis of D-p-methylsulfonylbenzenesser ethyl ester according to claim 1, wherein the palladium content of the Pd/C catalyst in the reduced phenylethane is 10%.
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