methyl (2R,3S)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoate

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 10.0 g of methyl (2R,3S)-3-t-butoxycarbonylamino-2-hydroxy-3-phenylpropionate, 0.334 g of pyridinium p-toluenesulphonate and 3.75 cm3 of trimethyl orthoformate in 70 cm3 of toluene is heated to reflux. 4 cm3 of solvent are distilled off. After cooling to a temperature in the region of 20° C. and filtration, the filtrate is concentrated to dryness under reduced pressure. The residue is taken up with 50 cm3 of hexane. The slurry obtained is filtered, rinsed and drained. 4.6 g of (4S,5R)-3-t-butoxycarbonyl-2-methoxy-4-phenyl-5-methoxycarbonyl-1,3-oxazolidine are thereby obtained in a 40% yield in the form of a mixture of diastereoisomers, the characteristics of which are as follows: 4 cm3 of solvent are distilled off the filtrate is concentrated to dryness under reduced pressure The slurry obtained is filtered rinsed

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 0.497 g of methyl (2R,3S)-3-t-butoxycarbonylamino-2-hydroxy-3-phenylpropionate, 0.012 g of pyridinum b-toluenesulphonate and 0.295 g of 2,4-dimethoxybenzaldehyde in 20 cm3 of anhydrous toluene is heated to reflux for 24 hours. The water formed during the reaction is removed by means of a Dean and Stark apparatus. After cooling to a temperature in the region of 20° C., the solution is washed with 37% (w/w) aqueous sodium hydrogen sulphite solution and then with saturated aqueous sodium bicarbonate solution. After concentration of the organic phase under reduced pressure, 0.700 g of (4S,5R)-3-t-butoxycarbonyl-2-(2,4-dimethoxyphenyl)-4-phenyl-5-methoxycarbonyl-1,3-oxazolidine is obtained in an 80% yield in the form of a virtually equimolecular mixture of the diastereo-isomeric forms A and B, the characteristics of which are as follows: to reflux for 24 hours is removed by means of a Dean and Stark apparatus the solution is washed with 37% (w/w) aqueous sodium hydrogen sulphite solution

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3.0 g of methyl (2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionate, of 5 cm3 of chloral and of 0.05 g of pyridinium p-toluenesulphonate in 40 cm3 of anhydrous toluene is heated at reflux with distillation of the solvent. 15 cm3 of solvent are distilled and then 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added. 20 cm3 of solvent are distilled and then 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added. 25 cm3 of solvent are distilled and then the solution is cooled to a temperature in the region of 20° C. The organic solution is washed with water (2 times 50 cm3), dried over sodium sulphate and concentrated to dryness under reduced pressure at approximately 50° C. The residue obtained is purified by liquid chromatography on silica gel, the eluent being an ethyl acetate/cyclohexane (1/3 by volume) mixture. There are thus obtained, with a yield of 91%, 3.0 g of (4S,5R)-5-methoxycarbonyl-4-phenyl-2-trichloromethyl-1,3-oxazolidine whose characteristics are the following: at reflux with distillation of the solvent 15 cm3 of solvent are distilled 5 cm3 of chloral and 0.05 g of pyridinium p-toluenesulphonate are added 20 cm3 of solvent are distilled 5 cm3 of chloral as well as 30 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled 5 cm3 of chloral and 35 cm3 of anhydrous toluene are added 25 cm3 of solvent are distilled The organic solution is washed with water (2 times 50 cm3) dried over sodium sulphate concentrated to dryness under reduced pressure at approximately 50° C The residue obtained is purified by liquid chromatography on silica gel