3-Thiophenecarboxylic acid, 2-amino-4-(3,4-dimethoxyphenyl)- synthesis

Yield:899690-79-0 40%

Reaction Conditions:

with water;potassium hydroxide in ethanol at 85; for 5 h;

Steps:

2-Amino-4-(3,4-dimethoxyphenyl)thiophene-3-carboxylic acid (24b).

At room temperature a solution of KOH (45 mg, 0.81 mmol) in water (1.5 mL) was added to a stirred solution of ethyl ester 1 (10 mg, 0.032 mmol) in ethanol (1.5 mL). The mixture was heated at 85°C for 5 h and then concentrated. The residue was treated with 810 μL of 1 M aqueous HCl in ether. The mixture was concentrated and the residue was suspended in dichloromethane and filtered. The filtrate was concentrated to a brown film that was purified by preparative TLC eluting with ethyl acetate/hexane (3:2) to give 24b as a yellow solid (3.6 mg, 40%); R_f 0.08 (1:1 ethyl acetate/hexane): ¹H NMR (400 MHz, CDCl₃) δ 7.66 (s, 1H), 7.49 (d, J = 6.5 Hz, 1H), 6.98 (d, J = 8.7 Hz, 1H), 4.57 (s, 2H), 3.97 (s, 3H), 3.96 (s, 3H).

References:

Titchenell, Paul M.;Hollis Showalter;Pons, Jean-Fran?ois;Barber, Alistair J.;Jin, Yafei;Antonetti, David A. [Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,# 10,p. 3034 - 3038] Location in patent:supporting information