(3S,5R)-1-benzyl-3,5-dimethylpiperidin-4-one

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

Procedure: The crude cis:trans mixture of 1-benzyl-3,5-dimethylpiperidin-4-one (typically 6:1 cis:trans) (45 g) was added to a 5% solution of sodium methoxide in methanol (500 mL) and stirred at room temperature for 6 hours. Saturated aqueous ammonium chloride (30 mL) was added and the mixture stirred for a further 30 minutes at room temperature. The mixture was evaporated to dryness and then redissolved in dichloromethane (500 mL). The insoluble solids were filtered off and the solvent was then evaporated to give an enriched mixture 96:4 cis:trans by 1H NMR (quantitative mass recovery). Longer reaction times did not give any further enrichment. If required, pure cis-product could then be obtained by chromatographic purification as described above. the mixture stirred for a further 30 minutes at room temperature The mixture was evaporated to dryness redissolved in dichloromethane (500 mL) The insoluble solids were filtered off the solvent was then evaporated to give an enriched mixture 96:4 cis Longer reaction times did not give any further enrichment pure cis-product could then be obtained by chromatographic purification

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of the crude dimethyl 1-benzyl-3,5-dimethyl-4-oxopiperidine-3,5-dicarboxylate (786.0 g, ca. 2.3 mol) and 1M hydrochloric acid solution (11.5 L) was refluxed for 24 hours. The reaction mixture was cooled to 10° C. and 25% wt. aqueous sodium hydroxide solution (1.92 kg) was added slowly. The mixture was extracted with dichloromethane (4×4 L), and the combined organic extracts concentrated to dryness to give the crude (3R,5S)-1-benzyl-3,5-dimethylpiperidin-4-one (475 g) as a light brown oil. The 1H NMR indicated that it was a 6:1 desired: undesired diastereomeric mixture. was refluxed for 24 hours The mixture was extracted with dichloromethane (4×4 L) the combined organic extracts concentrated to dryness