4-Methylmorpholine → (8aS,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 660 g of the d-10-camphorsulfonic acid salt of (8aS,12aS,13aS)-3-methoxy-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one (IA) in 8 litres of methylene chloride and 404 g of N-methylmorpholine was cooled in an ice bath to 10° C. and 153 ml of methanesulfonyl chloride was added over 30 minutes, allowing the temperature to rise to 16° C. The mixture was stirred at 10°-16° C. for 90 minutes, then washed sequentially with water, IN hydrochloric acid, and water. The organic layer was dried over sodium sulfate and the solvent removed under reduced pressure. The residue was crystallized from methanol to give (8aS,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one, m.p. 138°-140° C.

Provenance & Evidence