1-(3-Chlorophenyl)ethanone → HCID 118069401, compound

Participants

Reaction Conditions

Reaction Steps

Under an atmosphere of nitrogen, a solution of 3′-chloroacetophenone (1.015 mL, 7.82 mmol) in anhydrous diethyl ether (50 mL) was allowed to cool to −78° C. for 15 minutes prior to the slow addition of a 1.0 M solution of LHMDS (8.60 mL, 8.60 mmol) in THF. The enolate formation was allowed to stir for 45 minutes at −78° C., after which di-tert-butyl oxalate (1.898 g, 9.38 mmol) was added as a single portion. The pale yellow reaction mixture was allowed to warm to RT and stir for 18 hours. The dark-green solution was then quenched with 50 mL of a 1.0 M aq. solution of HCl. The two layers were separated and the aq. layer was extracted twice more with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure to afford an orange oil. The crude reaction mixture was purified by silica gel chromatography (40 g REDISEP® column, eluting with a gradient from 100% hexanes to 80:20 hexanes:EtOAc solution). Fractions containing the product were combined and evaporated to afford Intermediate A129A (2.17 g, 98%) as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.94-7.99 (1H, m), 7.86 (1H, dt, J=7.78, 1.38 Hz), 7.58 (1H, ddd, J=7.97, 2.20, 1.13 Hz), 7.43-7.49 (1H, m), 6.94-6.99 (1H, m), 1.58-1.63 (9H, m).

Provenance & Evidence