ethyl N-benzylcarbamate

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzylurethane (15.0 g, 83.9 mmol) was dissolved in dimethyl sulfoxide (40 mL), and thereto were added cesium fluoride (1.16 g, 7.63 mmol) and (S)-4-methoxymethyl-1,3- dioxolan-2-one (10.0 g, 76.3 mmol, optical purity 98.4%ee), in order. The mixture was stirred for 28 hours at 140° C. under an atmosphere of argon. After filtering off the insoluble materials, the filtrate was condensed in vacuo, and the residue was purified by silica gel chromatography to give the subject (R)-3-benzyl-5-methoxymethyloxazolidin-2-one (14.1 g, yield 83.5%, optical purity 98.2%ee). After filtering off the insoluble materials condensed in vacuo the residue was purified by silica gel chromatography

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzylurethane (15.0 g, 83.9 mmol) was dissolved in dimethyl sulfoxide (40 mL), and thereto were added cesium fluoride (1.16 g, 7.63 mmol) and (S)-4-methoxymethyl-1,3- dioxolan-2-one (10.0 g, 76.3 mmol, optical purity 98.4%ee), in order. The mixture was stirred for 28 hours at 140° C. under an atmosphere of argon. After filtering off the insoluble materials, the filtrate was condensed in vacuo, and the residue was purified by silica gel chromatography to give the subject (R)-3-benzyl-5-methoxymethyloxazolidin-2-one (14.1 g, yield 83.5%, optical purity 98.2%ee). After filtering off the insoluble materials condensed in vacuo the residue was purified by silica gel chromatography

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

Procedure: 288 g of ethyl pyruvate, 250 g of benzylurethane, 2.5 g of p-toluenesulphonic acid and 1 g of hydroquinone are introduced into 2.5 l of toluene and refluxed for 9 h in a water separator. The reaction solution is then filtered through silica gel and washed with 500 ml of toluene. The filtrate is treated with 1 g of hydroquinone and concentrated to the greatest possible extent on a rotary evaporator. 376 g of ethyl N-benzyloxycarbonyl-2-amino-acrylate are obtained as an oil, which according to HPLC has a purity of about 90%. The reaction solution is then filtered through silica gel washed with 500 ml of toluene The filtrate is treated with 1 g of hydroquinone concentrated to the greatest possible extent on a rotary evaporator

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

Procedure: 288 g of ethyl pyruvate, 250 g of benzylurethane, 2.5 g of p-toluenesulphonic acid and 1 g of hydroquinone are introduced into 2.5 l of toluene and refluxed for 9 h in a water separator. The reaction solution is then filtered through silica gel and washed with 500 ml of toluene. The filtrate is treated with 1 g of hydroquinone and concentrated to the greatest possible extent on a rotary evaporator. 376 g of ethyl N-benzyloxycarbonyl-2-amino-acrylate are obtained as an oil, which according to HPLC has a purity of about 90%. The reaction solution is then filtered through silica gel washed with 500 ml of toluene The filtrate is treated with 1 g of hydroquinone concentrated to the greatest possible extent on a rotary evaporator

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The benzylurethane from Reference Example 3 (5.54 g, 12.76 mmol ) in 50 ml dry THF was cooled to −70° C. under nitrogen and 8.80 ml of 1.6M nBuLi in hexanes (14.08 mmol ) added dropwise at the same temperature. After 20 minutes at the same temperature a solution of (R)-glycidyl butyrate (2.00 g, 13.88 mmol in 5 ml THF) was added dropwise and the mixture stirred for 30 minutes at −70° C., and then stirred to ambient temperature overnight. After quenching with 100 ml 10% ammonium chloride, the mixture was extracted with EtOAc and usual work-up to give an oily solid, which was purified by flash chromatography (Merck C60 silica, 5% MeOH/dichloromethane eluant) to give a crystalline solid (4.40 g, 86%). MS: ESP+ (M+H)=401. was cooled to −70° C. under nitrogen stirred to ambient temperature overnight After quenching with 100 ml 10% ammonium chloride the mixture was extracted with EtOAc and usual work-up to give an oily solid, which was purified by flash chromatography (Merck C60 silica, 5% MeOH/dichloromethane eluant)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzylurethane (15.0 g, 83.9 mmol) was dissolved in dimethyl sulfoxide (40 mL), and thereto were added cesium fluoride (1.16 g, 7.63 mmol) and (S)-4-methoxymethyl-1,3- dioxolan-2-one (10.0 g, 76.3 mmol, optical purity 98.4%ee), in order. The mixture was stirred for 28 hours at 140° C. under an atmosphere of argon. After filtering off the insoluble materials, the filtrate was condensed in vacuo, and the residue was purified by silica gel chromatography to give the subject (R)-3-benzyl-5-methoxymethyloxazolidin-2-one (14.1 g, yield 83.5%, optical purity 98.2%ee). After filtering off the insoluble materials condensed in vacuo the residue was purified by silica gel chromatography

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

Procedure: 288 g of ethyl pyruvate, 250 g of benzylurethane, 2.5 g of p-toluenesulphonic acid and 1 g of hydroquinone are introduced into 2.5 l of toluene and refluxed for 9 h in a water separator. The reaction solution is then filtered through silica gel and washed with 500 ml of toluene. The filtrate is treated with 1 g of hydroquinone and concentrated to the greatest possible extent on a rotary evaporator. 376 g of ethyl N-benzyloxycarbonyl-2-amino-acrylate are obtained as an oil, which according to HPLC has a purity of about 90%. The reaction solution is then filtered through silica gel washed with 500 ml of toluene The filtrate is treated with 1 g of hydroquinone concentrated to the greatest possible extent on a rotary evaporator