(5S)-5-(hydroxymethyl)-3,3-dimethylpyrrolidin-2-one

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

Procedure: A mixture of 27.15 g I.46 (3,3,6,6-tetramethyl-tetrahydro-pyrrolo[1,2-c]oxazol-5-one) and 0.282 g p-toluenesulfonic acid in 500 ml methanol was stirred at reflux overnight. The mixture was concentrated. Additional 500 ml methanol and 2.8 g p-toluenesulfonic acid were added and the mixture was stirred 4 h at reflux. The mixture was diluted with water and treated with sodium carbonate to obtain a basic pH. The organic layer was separated, dried with magnesium sulfate and concentrated to give 1 g (60% content; 3% of theory) at reflux overnight The mixture was concentrated Additional 500 ml methanol and 2.8 g p-toluenesulfonic acid were added the mixture was stirred 4 h at reflux The mixture was diluted with water treated with sodium carbonate to obtain a basic pH The organic layer was separated dried with magnesium sulfate concentrated to give 1 g (60% content; 3% of theory)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 32.35 g (226 mmol) of (S)4,4-dimethyl-2-hydroxymethyl-5-oxopyrrolidine in 300 ml of tetrahydrofuran was added dropwise over a period of 20 minutes with ice-cooling and stirring to keep the temperature between 8 and 17° C., to a suspension of 25.72 g (678 mmol) of lithium aluminum hydride in 500 ml of tetrahydrofuran. The resulting mixture was then heated under reflux for 7 hours, at the end of which time it was cooled to 0° C. and 103 ml of a 4% aqueous solution of sodium hydroxide were added carefully thereto. Any insoluble material was removed by filtration and the filtrate was concentrated by evaporation under reduced pressure. The residue thus obtained was dissolved in 500 ml of methylene chloride and then 40.94 ml (294 mmol) of triethylamine were added, followed by the further addition of 38.71 ml (271 mmol) of benzyloxycarbonyl chloride with ice-cooling and stirring. The resulting mixture was stirred for 1 hour at the same temperature and then stirred for a further 1 hour at room temperature. At the end of this time, a saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture, and it was then extracted with methylene chloride. The organic extract was washed with water, dried over anhydrous magnesium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was purified by chromatography on a silica gel column using a 1:1 by volume mixture of hexane and ethyl acetate as the eluant to afford 43.97 g (yield: 74%) of the title compound as a colorless oil. cooling the temperature between 8 and 17° C. The resulting mixture was then heated under reflux for 7 hours, at the end of which time it Any insoluble material was removed by filtration the filtrate was concentrated by evaporation under reduced pressure The residue thus obtained cooling stirring The resulting mixture was stirred for 1 hour at the same temperature stirred for a further 1 hour at room temperature was then extracted with methylene chloride The organic extract was washed with water dried over anhydrous magnesium sulfate concentrated by evaporation under reduced pressure The resulting residue was purified by chromatography on a silica gel column by volume mixture of hexane and ethyl acetate as the eluant