HCID 57974098, compound → Methyl 3,5-difluoro-α,α-dimethyl-δ-oxobenzenepentanoate

Participants

Reaction Steps

To a solution of methyl 5-[methoxy(methyl)amino]-2,2-dimethyl-5-oxopentanoate from Step C (4.68 g, 21.6 mmol) in THF (47 mL), cooled to 0° C., was added 3,5-difluorophenylmagnesium bromide (65 mL, 0.5 M in THF, 32.3 mmol) over 30 min. The reaction mixture was allowed to stir at ambient temperature for 2 h, then re-cooled to 0° C. Additional 3,5-difluorophenylmagnesium bromide (50 mL, 0.5 M in THF, 25.0 mmol) was added over 30 min. After a further 3 h at 0° C., the reaction was quenched by the rapid addition of a cold (0° C.) solution of EtOH (71 mL) and conc. HCl (5.0 mL). The resulting mixture was then diluted with water (200 mL) and diethyl ether (400 mL). The organics were washed with water (3×200 mL) and brine (100 mL), then dried over sodium sulfate, filtered, and concentrated in vacuo to give a residue. This residue was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:hexanes—50:50 to 100:0, to give the title compound. MS: m/z=239 (M−OCH3).

Provenance & Evidence