Diisopropylethylamine → 1-((1S,3R)-5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one

Participants

Reaction Steps

Dissolve (1S,3R)-5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline (1.85 g, 4.99 mmol) and 2-chloro-6-fluorophenylacetic acid (1.04 g, 5.49 mmol) in dichloromethane (50 mL). Add 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (2.85 g, 7.49 mmol) and diisopropylethylamine (1.3 mL, 7.49 mmol) at rt. Stir 3 hours. Add water and extract with dichloromethane three times. Combine the dichloromethane extracts, dry over sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Purify the residue by silica gel chromatography, eluting with ethyl acetate: hexanes (gradient, 5-60%) to give the title compound as a white foam (2.2 g, 4.07 mmol). MS (m/z): 540.2 (M+1).

Provenance & Evidence