(R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-3,4-dihydroisoquinoline → (1S,3R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline

Participants

Reaction Conditions

Reaction Steps

Dissolve (3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3,4 dihydroisoquinoline (3.4 g, 9.59 mmol) in diethyl ether (160 mL). Cool to −78° C. on a dry ice-acetone bath. Add methylmagnesium chloride (26.9 mL, 80.6 mmol, 3M in THF) dropwise. Warm the reaction mixture slowly to room temperature and stir overnight. Quench with saturated ammonium chloride solution slowly. Extract with dichloromethane and dry over sodium sulfate, filter, and concentrate under reduced pressure. Combine with the crude product from a substantially same reaction run with 1.73 mmol of (3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3,4 dihydroisoquinoline. Purify the combined residues by silica gel chromatography eluting with ethyl acetate: hexanes (5-65% gradient) to give the title compound (3.78 g, 10.2 mmol). MS (m/z): 370 (M+1).

Provenance & Evidence