Hydrochloric Acid → Methyl 2-(4-fluorophenyl)-2-oxoacetate

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Reaction Conditions

Reaction Steps

Dimethyl oxalate (5.90 g, 50 mmol) was dissolved in THF (50 mL) and ether (50 mL) in a 3-neck round bottom flask fitted with a mechanical stirrer. The solution was stirred vigorously at −65° C. as a 1.0 M THF solution of 4-fluorophenylmagnesium bromide (60 mL, 60 mmol) was added dropwise over 40 min. The mixture was stirred 30 min. at −65° C. and allowed to warm to −20° C. over 30 min. before being poured into 2 N HCl (50 mL) with stirring. The layers were separated and the aq. layer was extracted with ether (3×50 mL). The combined organic layers were washed with saturated aq. NaCl (2×50 mL), dried (Na2SO4), decanted, and evaporated. The residue was dissolved in EtOAc, dried (Na2SO4), filtered, and evaporated to give a yellow solid. The crude product was dissolved in warm hexane (25 mL), filtered, and cooled to −20° C. Filtration followed by washing with cold hexane (15 mL) gave 4.95 g of the title compound as light tan crystals. 1H NMR (500 MHz) δ 8.11 (dd, J=9.0,5.0,2H), 7.21 (t, J=9,22H), 4.00 (s, 3H); HPLC A: 2.59 min.

Provenance & Evidence