Hydrochloric Acid → HCID 66749017, compound

Participants

Reaction Steps

Ethyl 4-cyano-5-(morpholin-4-yl)-3-[1-(2-naphthyl)ethyl]thiophene-2-carboxylate (13.3 g, 31.6 mmol) in tetrahydrofuran (200 mL) and methanol (150 mL) was stirred until the mixture turned into a clear solution. To the solution was added 1.000 M sodium hydroxide in water (158 mL). The resulting turbid mixture was vigorously stirred at rt for 12 h. The volatiles were removed under reduced pressure, and the resulting aqueous solution was acidified by addition of 12.0 M of hydrochloric acid in water (15.9 mL, 191 mmol) at 0° C., and then extracted with EtOAc (×3). The combined organic layers were washed with 1M HCl soln, dried, and concentrated to provide 4-cyano-5-(morpholin-4-yl)-3-[1-(2-naphthyl)ethyl]thiophene-2-carboxylic acid as a white solid (12.1 g, 97.5% yield). 250 mg of the racemic mixture was purified on chiral prep HPLC to provide each enantiomer (115 mg each, >95% ee) (OJ column, elution with 85/5/10/0.1% hexane/iPrOH/EtOH/Et2NH). LCMS: (AA) ES+ 393; 1H NMR (400 MHz, MeOD) δ 7.85-7.76 (m, 3H), 7.76-7.71 (d, J=8.6 Hz, 1H), 7.49-7.38 (m, 2H), 7.38-7.29 (dd, J=8.5, 1.7 Hz, 1H), 5.90-5.74 (q, J=7.3 Hz, 1H), 3.82-3.69 (m, 4H), 3.52-3.43 (dd, J=5.8, 4.0 Hz, 4H), 1.91-1.80 (d, J=7.3 Hz, 3H).

Provenance & Evidence