Potassium Carbonate → 4-[3-(Benzyloxy)-4-methoxyphenyl]pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

NaBH4 (14 g, 104.5 mmol) was slowly added to a mixture of NiCl2-6H2O (8.3 g, 34.8 mmol) in MeOH (750 mL). The mixture was stirred for 30 minutes at 0° C. and then a solution of methyl 3-(3-benzyloxy-4-methoxyphenyl)-4-nitrobutanoate (25 g) in 500 mL of MeOH was added. An additional 8.3 g (34.8 mmol) of NiCl2-6H2O was then added, followed by the slow portion-wise addition of NaBH4 (9.2 g, 243 mmol). The resulting mixture stirred at 0° C. for 1 hour and then K2CO3 (150 g) was added in one portion. The mixture was allowed to warm to room temperature and stirred for 18 hours. The suspension was then filtered through celite, washed with MeOH (2×1000 mL) and concentrated. The residue was dissolved in EtOAc (2000 mL) and the organic fraction was successively washed with H2O (200 mL) and brine (250 mL), dried (Na2SO4) and concentrated to a solid. Trituration with hexanes/EtOAc provided 13 g of 4-(3-benzyloxy-4-methoxyphenyl)-2-pyrrolidone. An additional 2.3 g of product was obtained by extracting the aqueous fractions with EtOAc and combining this with the trituration solvent, concentrating and triturating with EtOAc/hexanes. Total yield was 15.3 g (74%). 1H NMR (400 MHz, CDCl3) δ 7.44-7.26 (m, 5H), 6.87-6.70 (m, 3H), 5.75 (bs, 1H), 5.14 (s, 2H), 3.87 (s, 3H), 3.70-3.50 (m, 2H), 3.28 (t, 1H), 2.70-2.63 (m, 1H), 2.42-2.35 (m, 1H).

Provenance & Evidence