4-(methoxycarbonyl)thiophene-3-carboxylic acid synthesis

Yield:4282-30-8 87%

Reaction Conditions:

with sodium hydroxide in methanol at 20;

Steps:

2.19 4.2.19 4-(Methoxycarbonyl)thiophene-3-carboxylic acid (26)

General procedure: To a solution of dimethyl thiophene-3,4-dicarboxylate (25, 825 mg, 4.12 mmol) in methanol (10 mL) was added sodium hydroxide (165 mg, 4.12 mmol) and stirred overnight at room temperature. Solvent was removed, and the crude product was partitioned between diethyl ether (15 mL) and water (15 mL). The aqueous phase was extracted with ether (3 * 10 mL), and the combined organic layers were discarded. The aqueous phase was adjusted to pH 1 with hydrochloric acid (2 N) and extracted with EtOAc (3 * 10 mL). The combined organics were washed with brine (10 mL), dried (Na₂SO₄), and concentrated under reduced pressure to yield the desired product as a white solid (667 mg, 87%). ¹H NMR (500 MHz, CDCl₃) δ 8.49 (d, J = 3.7 Hz, 1H), 8.37 (d, J = 3.7 Hz, 1H), 4.04 (s, 4H). ¹³C NMR (126 MHz, CDCl₃) δ 166.95, 161.38, 139.26, 138.45, 133.68, 128.05, 53.96. HRMS (ESI): Calcd for C₇H₆O₄S [M-H]^- 184.9914; found 184.9900.

References:

Hawker, Dustin D.;Silverman, Richard B. [Bioorganic and Medicinal Chemistry,2012,vol. 20,# 19,p. 5763 - 5773]