Boron trifluoride etherate → Tert-butyl 4-(adamantan-2-yl(hydroxy)methyl)-3-chlorobenzoate

Participants

Reaction Steps

To a solution of tert-butyl 4-bromo-3-chlorobenzoate (0.875 g, 3.00 mmol) in tetrahydrofuran (5 mL) was added isopropylmagnesium chloride lithium chloride complex (1.3 M solution in anhydrous tetrahydrofuran, 2.78 mL, 3.61 mmol) at −40° C. The reaction was allowed to warm to ambient temperature and stirred for 1 hour (solution A). In a separate flask, a solution of spiro(adamantane-2,2′-oxirane) (0.492 g, 3.00 mmol) in anhydrous tetrahydrofuran (5 mL) was treated with boron trifluoride diethyl etherate (0.38 mL, 3.0 mmol) at 0° C. for 30 minutes (solution B). Solution A was then transferred via cannula to solution B at 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred for 16 hours. After quenched with saturated ammonium chloride solution (5 mL), the mixture was extracted with ethyl acetate (3×10 mL). The combined organic phase was dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo gave a residue which was purified by silica gel column chromatography using 0-100% ethyl acetate in hexanes as eluent to afford the title compound as a colorless solid (0.32 g, 33%): 1H NMR (300 MHz, DMSO-d6) δ 7.84 (dd, J=8.1, 1.4 Hz, 1H), 7.80 (d, J=1.5 Hz, 1H), 7.64 (d, J=8.1 Hz, 1H), 5.44 (br s, 1H), 5.18 (d, J=10.3 Hz, 1H), 2.36-2.29 (m, 1H), 2.06-1.34 (m, 22H), 1.08-1.01 (m, 1H); MS (ES+) m/z 359.2, 361.2 (M−17).

Provenance & Evidence