(S)-3-羟基-3-苯基丙酸甲酯

反应条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At room temperature, a three-neck flask equipped with a reflux condenser, internal thermometer, dropping funnel and stirrer under protective nitrogen gas was initially charged with 5 g of zinc dust (77 mmol) in 30 ml of tetrahydrofuran. After 1.2 ml of trimethylchlorosilane had been added, the mixture was heated to 55 C for 15 min, and 10.9 g of methyl bromoacetate (71 mmol) were subsequently added dropwise undiluted while refluxing at 45° C. within 7 min. The mixture was then stirred for 10 min. After cooling to 10 C, 30 ml of tetrahydrofuran were added and 17 g of (−)-sparteine (72 mmol) were subsequently added undiluted at 0 C, and the temperature rose to 5 C. The mixture was cooled to 15 C and 6.4 g of benzaldehyde (60 mmol) were added undiluted. The reaction mixture was subsequently stirred at 15 C for 20 h, then acidified at this temperature with 35 ml of 20% hydrochloric acid to a pH of 3 and stirred for 10 min, and the temperature of the mixture rose to 0 C. 150 ml of water were then added. Precipitated sparteine salt was filtered off with suction and washed twice with 40 ml of ethyl acetate each time. After removing the organic phase, the aqueous phase was extracted with 50 ml of ethyl acetate and the organic phase was subsequently removed. The organic phase was then stirred with 20 ml of concentrated ammonia solution at −10° C. for 5 min. After phase separation, drying and removal of solvent under reduced pressure, methyl (S)-(−)-3-hydroxy-3-phenylpropionate was obtained in a yield of 10.5 g (97% of theory) and a purity of >95% and 89% ee (HPLC). At room temperature, a three-neck flask equipped with a reflux condenser the mixture was heated to 55 C for 15 min were added were added The reaction mixture was subsequently stirred at 15 C for 20 h stirred for 10 min Precipitated sparteine salt was filtered off with suction washed twice with 40 ml of ethyl acetate each time After removing the organic phase the aqueous phase was extracted with 50 ml of ethyl acetate the organic phase was subsequently removed The organic phase was then stirred with 20 ml of concentrated ammonia solution at −10° C. for 5 min After phase separation drying removal of solvent under reduced pressure

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Into a 1-L autoclave was introduced methanol (360 mL) in a nitrogen stream. Then, [{RuCl((R)-SEGPHOS)}2(μ-Cl)3][Me2NH2] (82 mg: 0.1 mmol) and methyl benzoylacetate (178 g: 1.0 mol) were added. After hydrogen (4.0 MPa) was forced into the autoclave, the reaction mixture was heated to 80° C. and stirred for 5.5 hours to carry out asymmetric hydrogenation reaction. After cooling, methanol was removed from the reaction mixture, and the residue was distilled under reduced pressure (94-99° C./133 Pa) to obtain 170.6 g (yield, 95.3%) of methyl (S)-3-hydroxy-3-phenylpropionate. The asymmetric yield thereof was determined with the HPLC (CHIRALCEL OD-H, 4.6 mm×250 mm; hexane/isopropyl alcohol=95/5; flow rate, 1.0 mL/min; detection wavelength, UV-254 nm), and was found to be 97.2%. hydrogenation reaction After cooling methanol was removed from the reaction mixture the residue was distilled under reduced pressure (94-99° C./133 Pa)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 1 liter four-necked flask were charged 200 g (1.11 mol) of methyl (S)-3-hydroxy-3-phenylpropionate (optical purity: 87%e.e.), 77.8 g (1.56 mol) of hydrazine monohydrate, and 400 ml of methanol, and the mixture was heated at 70° C. for 3 hours. The reaction mixture was cooled to 5° C. with ice-water, followed by filtration. The collected crystals were dissolved in 4.7 liter of methanol while hot and cooled to 5° C. The crystals thus precipitated were collected by filtration and dried to give 148 g (74%) of the title compound. Melting point: 179.5° C. Optical purity: >99.9%e.e. followed by filtration The collected crystals were dissolved in 4.7 liter of methanol while hot and cooled to 5° C The crystals thus precipitated were collected by filtration dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 1 liter autoclave was charged a mixture of 0.84 g of (1.0 mmol) of Ru2Cl4((R)-Tol-BINAP)2.NET3, 178 g (1.00 mol) of methyl benzoylacetate, and 500 ml of methanol, and the mixture was stirred at 50° C. under a hydrogen pressure of 1000 kPa for 16 hours. The solvent was evaporated under reduced pressure, and the residue was distilled under reduced pressure (99° C./100 Pa.) to yield 171 g (95%) of the title compound as liquid. Optical purity: 87%e.e. In a 1 liter autoclave was charged The solvent was evaporated under reduced pressure the residue was distilled under reduced pressure (99° C./100 Pa.)

反应条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At room temperature, a three-neck flask equipped with a reflux condenser, internal thermometer, dropping funnel and stirrer under protective nitrogen gas was initially charged with 5 g of zinc dust (77 mmol) in 30 ml of tetrahydrofuran. After 1.2 ml of trimethylchlorosilane had been added, the mixture was heated to 55 C for 15 min, and 10.9 g of methyl bromoacetate (71 mmol) were subsequently added dropwise undiluted while refluxing at 45° C. within 7 min. The mixture was then stirred for 10 min. After cooling to 10 C, 30 ml of tetrahydrofuran were added and 17 g of (−)-sparteine (72 mmol) were subsequently added undiluted at 0 C, and the temperature rose to 5 C. The mixture was cooled to 15 C and 6.4 g of benzaldehyde (60 mmol) were added undiluted. The reaction mixture was subsequently stirred at 15 C for 20 h, then acidified at this temperature with 35 ml of 20% hydrochloric acid to a pH of 3 and stirred for 10 min, and the temperature of the mixture rose to 0 C. 150 ml of water were then added. Precipitated sparteine salt was filtered off with suction and washed twice with 40 ml of ethyl acetate each time. After removing the organic phase, the aqueous phase was extracted with 50 ml of ethyl acetate and the organic phase was subsequently removed. The organic phase was then stirred with 20 ml of concentrated ammonia solution at −10° C. for 5 min. After phase separation, drying and removal of solvent under reduced pressure, methyl (S)-(−)-3-hydroxy-3-phenylpropionate was obtained in a yield of 10.5 g (97% of theory) and a purity of >95% and 89% ee (HPLC). At room temperature, a three-neck flask equipped with a reflux condenser the mixture was heated to 55 C for 15 min were added were added The reaction mixture was subsequently stirred at 15 C for 20 h stirred for 10 min Precipitated sparteine salt was filtered off with suction washed twice with 40 ml of ethyl acetate each time After removing the organic phase the aqueous phase was extracted with 50 ml of ethyl acetate the organic phase was subsequently removed The organic phase was then stirred with 20 ml of concentrated ammonia solution at −10° C. for 5 min After phase separation drying removal of solvent under reduced pressure