Acetaldehyde → Methyl 4-(adamantan-1-ylmethoxy)-2-fluoro-5-(1-hydroxyethyl)benzoate

Participants

Reaction Conditions

Reaction Steps

To a mixture of methyl 4-(adamantan-1-ylmethoxy)-2-fluoro-5-iodobenzoate (1.25 g, 2.80 mmol) in anhydrous tetrahydrofuran (10 mL) was added isopropylmagnesium chloride lithium chloride complex (1.3 M solution in tetrahydrofuran, 3.2 mL, 4.20 mmol) at −40° C. The reaction mixture was stirred for 1 hour at −40° C., after which acetaldehyde (0.79 mL, 14.10 mmol) was added. The reaction mixture was allowed to warm to ambient temperature, stirred for 16 hours and then was quenched by addition of saturated ammonium chloride solution (10 mL). The mixture was extracted with ethyl acetate (2×50 mL) and the combined organic phase was washed with brine (10 mL), 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 0-35% ethyl acetate in hexanes as eluent to afford the title compound as an amorphous solid (0.76 g, 75%): 1H NMR (300 MHz, CDCl3) δ 7.96 (d, J=8.5 Hz, 1H), 6.58 (d, J=12.7 Hz, 1H), 5.16-5.06 (m, 1H), 3.88 (s, 3H), 3.55 (d, J=8.9 Hz, 1H), 3.52 (d, J=9.3 Hz, 1H), 2.27 (d, J=4.8 Hz, 1H), 2.08-1.98 (m, 3H), 1.83-1.61 (m, 12H), 1.49 (d, J=6.5 Hz, 3H); MS (ES+) m/z 345.2 (M−17).

Provenance & Evidence