Sodium Hydroxide → 4-Cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylic acid

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Reaction Steps

To a solution of ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate (0.211 g, 0.453 mmol) in tetrahydrofuran (8.00 mL) was added 1.000 M of sodium hydroxide in water (10.0 mL) and methanol (4.00 mL). The resulting mixture was stirred at room temp over 3 hrs. The volatiles were removed under reduced pressure, and the resulting mixture was acidified with conc. HCl soln to pH ˜2, and extracted with EtOAc (×3). The combined org layer was dried and concentrated to provide a purple syrup. Purification of the crude mixture on HPLC (AA, reverse phase) provided 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylic acid as a white solid (63 mg, 31.8% yield). LCMS: (AA) ES− 391, 393, 395; 1H NMR (400 MHz, MeOD) δ 7.54-7.46 (d, J=1.6 Hz, 1H), 7.45-7.35 (d, J=8.4 Hz, 1H), 7.34-7.24 (dd, J=8.4, 1.6 Hz, 1H), 5.88-5.68 (m, 2H), 5.16-5.05 (dd, J=17.1, 1.7 Hz, 1H), 5.00-4.92 (m, 1H), 3.82-3.71 (t, J=4.8 Hz, 4H), 3.51-3.40 (t, J=4.8 Hz, 4H), 3.05-2.95 (m, 2H).

Provenance & Evidence