2-Methyl-3-buten-2-ol → (3E)-4-[(1S,3R)-3-[[[(1,1-Dimethylethyl)dimethylsilyl]oxy]methyl]-1,2,3,4-tetrahydro-1-methyl-5-isoquinolinyl]-2-methyl-3-buten-2-ol

Participants

Reaction Conditions

Reaction Steps

Add (1S,3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (310 g, 723.83 mmol) and 2-methylbut-3-en-2-ol (508.95 g, 5.79 mol) to N,N-dimethylformamide (1.08 L) in an appropriate vessel and degas by bubbling nitrogen through the solution for 10 minutes. Add potassium carbonate (315.12 g, 2.28 mol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (15.32 g, 36.19 mmol) and palladium (II) acetate (8.29 g, 36.19 mmol) and degas by bubbling nitrogen through the mixture for 15 minutes then heat to 125° C. After 16 hours, cool the mixture to 20° C. and dilute with ethyl acetate (1.5 L) and water (2.5 L). Wash the ethyl acetate layer with brine (2.5 L), then dry over sodium sulfate and concentrate under reduced pressure to give a residue. Purify the residue by flash chromatography, eluting with 0-50% ethyl acetate in isohexanes to give the title compound (193 g, 459.1 mmol). MS (m/z): 376(M+1).

Provenance & Evidence