Imidazole → [(3R)-5-Bromo-1,2,3,4-tetrahydroisoquinolin-3-YL]methoxy-tert-butyl-dimethyl-silane

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Reaction Conditions

Reaction Steps

Add tert-butyldimethylchlorosilane (193.7 g, 1.29 mol) to a mixture of [(3R)-5-bromo-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol (148.9 g, 0.58 mol), 1H-imidazole (202.9 g, 2.92 mol), 4-dimethylaminopyridine (0.72 g, 5.84 mmol) and N,N-dimethylformamide (1.04 L) in dichlormethane (2.61 L) at 20° C. and stir in an appropriate vessel. After 3 hours, cool the mixture to 10° C. and add saturated aqueous ammonium chloride solution (1.3 L). Extract the aqueous with dichloromethane and wash the combined organic extracts with brine (2×2 L), dry over anhydrous sodium sulfate and concentrate under reduced pressure to give a residue. Dissolve the residue in methyl tert-butyl ether (1.5 L) and wash with brine (2×1 L). Dilute the organic phase with toluene (5 L) and concentrate under reduced pressure to give a residue. Add toluene (2.6 L) to the residue and concentrate under reduced pressure to give the title compound (210 g, 0.53 mol). MS (m/z). 356(M+1 (79Br)), 358(M+1 (81Br)).

Provenance & Evidence