Ethyl bromoacetate → 2-(3-(4-Fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Participants

Reaction Steps

To a suspension of 3-(4-fluorophenyl)pyrrolidin-2-one (Example 189B, 1.36 g, 7.59 mmol) in tetrahydrofuran was added potassium 2-methylpropan-2-olate (8.35 ml, 8.35 mmol). The reaction was allowed to stir for 30 minutes, during which time a yellow solution resulted. To the reaction was added ethyl 2-bromoacetate (0.92 ml, 8.35 mmol) and stirring was continued at room temperature. After stirring for 3 hours, the reaction was poured into a 1:1 mixture of ethyl acetate/1 N HCl (300 mL). The organic layer was separated, washed with brine (100 mL), dried over magnesium sulfate and concentrated. The residue was dissolved in minimal dichloromethane and loaded onto a GraceResolv 40 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes. The resulting ethyl ester intermediate was dissolved in methanol (10 mL) and treated with sodium hydroxide (7.59 mL, 15.18 mmol). After stirring for 1 hour, the reaction was poured into a 1:1 mixture of ethyl acetate/1 N HCl (300 mL). The organic layer was washed with brine (100 mL), dried over magnesium sulfate and concentrated to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 12.87 (s, 1H), 7.34-7.26 (m, 2H), 7.20-7.10 (m, 2H), 4.00 (s, 2H), 3.71 (t, J=9.0, 1H), 3.52-3.43 (m, 2H), 2.59-2.35 (m, 1H), 2.07-1.91 (m, 1H).

Provenance & Evidence