Methanol → Acetic acid, 2-[4-(4-bromophenyl)-4-hydroxycyclohexylidene]-, methyl ester

Participants

Reaction Steps

To a solution of NaH (60% dispersion in mineral oil, 70 mg, 1.7 mmol) in methanol (6.7 mL) was added trimethylphosphonoacetate (0.23 mL, 1.6 mmol) and the reaction was let stir at rt for 30 min. To the reaction was added 4-(4-bromophenyl)-4-hydroxycyclohexanone (360 mg, 1.3 mmol) and the reaction was let stir at rt for 20 h. The resulting reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried over MgSO4, filtered and concentrated by rotary evaporation in vacuo to afford 530 mg of a crude opaque oil. Purification of the crude material by column chromatography (25 g silica gel, 0-60% EtOAc:Hept, monitor 230 nm) afforded 51 mg (12%) of methyl 2-(4-(4-bromophenyl)-7-oxabicyclo[2.2.1]heptan-1-yl)acetate as a colorless oil (ESI-MS m/z: 327.1 [M+H]+, retention time 1.56 min (condition E)) and 275 mg (63%) of the title compound as a colorless oil (ESI-MS m/z: n/a [M+H]+, retention time 1.42 min (condition E)). 1H NMR (400 MHz, DMSO-d6): δ ppm 1.71-1.93 (m, 4H), 2.19 (d, J=13.1 Hz, 1H), 2.29-2.44 (m, 1H), 2.66 (td, J=12.6, 4.7 Hz, 1H), 3.56-3.69 (m, 4H), 5.24 (s, 1H), 5.72 (s, 1H), 7.41-7.52 (m, 4H). 13C NMR (100 MHz, DMSO-d6): δ ppm 166.1, 162.5, 148.7, 130.6, 127.1, 119.3, 112.6, 70.8, 50.6, 38.7, 32.4, 24.5.

Provenance & Evidence