(1S,5R)-2-氧代-3-氧代环[3.1.0]己烷-1-羧酸乙酯

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a reactor, ethanol (82.4 L) followed by ethyl (1S,5R)-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate (10.3 kg, 64.6 mol) were added and cooled to 10° C. Sodium borohydride (1.85 kg, 51.7 mol) was added in lots over a period of 1 hour by maintaining the reaction temperature between 10-15° C. The reaction temperature was raised to 20-25° C. and maintained for 1 hour. The progress of the reaction was monitored by HPLC. After completion of the reaction, the reaction mass was cooled to 0-5° C. The pH of the reaction mass was adjusted to 7.0 using 1.5 N aqueous HCl at 0-5° C. during 1 hour. Ethyl acetate (34.0 L) was added to the reaction mass and the solid was filtered. The clear filtrate was distilled under reduced pressure at 40-45° C. to remove most of the solvent and the concentrate was dissolved in dichloromethane (103.0 L). The dichloromethane layer was washed with water (2×10.5 L). The aqueous layer was re-extracted with dichloromethane (3×10.5 L). The dichloromethane layers were combined and washed with brine (1×15.0 L). The organic layer was collected and distilled to remove most of the solvent at 40-45° C. under reduced pressure. The concentrate was passed over silica gel 60-120 mesh plug column using petroleum ether followed by 100% ethyl acetate as eluent to afford 5.0 kg (47.4%) of the title compound (2c). were added by maintaining the reaction temperature between 10-15° C The reaction temperature was raised to 20-25° C. maintained for 1 hour After completion of the reaction the reaction mass was cooled to 0-5° C the solid was filtered The clear filtrate was distilled under reduced pressure at 40-45° C. to remove most of the solvent the concentrate was dissolved in dichloromethane (103.0 L) The dichloromethane layer was washed with water (2×10.5 L) The aqueous layer was re-extracted with dichloromethane (3×10.5 L) washed with brine (1×15.0 L) The organic layer was collected distilled to remove most of the solvent at 40-45° C. under reduced pressure

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a reactor, ethanol (82.4 L) followed by ethyl (1S,5R)-2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate (10.3 kg, 64.6 mol) were added and cooled to 10° C. Sodium borohydride (1.85 kg, 51.7 mol) was added in lots over a period of 1 hour by maintaining the reaction temperature between 10-15° C. The reaction temperature was raised to 20-25° C. and maintained for 1 hour. The progress of the reaction was monitored by HPLC. After completion of the reaction, the reaction mass was cooled to 0-5° C. The pH of the reaction mass was adjusted to 7.0 using 1.5 N aqueous HCl at 0-5° C. during 1 hour. Ethyl acetate (34.0 L) was added to the reaction mass and the solid was filtered. The clear filtrate was distilled under reduced pressure at 40-45° C. to remove most of the solvent and the concentrate was dissolved in dichloromethane (103.0 L). The dichloromethane layer was washed with water (2×10.5 L). The aqueous layer was re-extracted with dichloromethane (3×10.5 L). The dichloromethane layers were combined and washed with brine (1×15.0 L). The organic layer was collected and distilled to remove most of the solvent at 40-45° C. under reduced pressure. The concentrate was passed over silica gel 60-120 mesh plug column using petroleum ether followed by 100% ethyl acetate as eluent to afford 5.0 kg (47.4%) of the title compound (2c). were added by maintaining the reaction temperature between 10-15° C The reaction temperature was raised to 20-25° C. maintained for 1 hour After completion of the reaction the reaction mass was cooled to 0-5° C the solid was filtered The clear filtrate was distilled under reduced pressure at 40-45° C. to remove most of the solvent the concentrate was dissolved in dichloromethane (103.0 L) The dichloromethane layer was washed with water (2×10.5 L) The aqueous layer was re-extracted with dichloromethane (3×10.5 L) washed with brine (1×15.0 L) The organic layer was collected distilled to remove most of the solvent at 40-45° C. under reduced pressure