Tetrabutylammonium Fluoride → Mevidalen

Participants

Reaction Conditions

Reaction Steps

Add tetra-n-butylammonium fluoride (651.71 mL, 651.71 mmol, 1M in THF) to a solution of 1-[(1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-(3-hydroxy-3-methyl-butyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl]-2-(2,6-dichlorophenyl)ethanone (400 g, 566.71 mmol) in tetrahydrofuran (4 L) at 5° C. in an appropriate vessel. Heat the mixture to 20° C. and stir. After 3 hours, remove 3 L of tetrahydrofuran by concentrating under reduced pressure and dilute the residues with ethyl acetate (2.5 L). Wash the organics with saturated aqueous ammonium chloride (2 L), water (2 L) and brine (2×2 L). Dry the ethyl acetate solution over anhydrous sodium sulfate and concentrate under reduced pressure to give an oil. Dissolve this oil in 2-propanol (2.5 L) and concentrate under reduced pressure to give an oil. Purify by chiral SFC using AS-H column (50×250 mm, 5 micron particle size) eluting with 80% supercritical carbon dioxide and 20% of a 0.2% solution of diethylmethylamine in isopropyl alcohol at 280 g/min to give the title compound (182.8 g, 389.62 mmol). MS (m/z): 450.2 (M+1 (35C1)), 452.2 (M+1 (37Cl)). Optical rotation: [α]20D −39.4° (c=0.95, MeOH).

Provenance & Evidence