5-Thiazolecarboxylic acid, 2-methyl- → HCID 66643644, compound

Participants

Reaction Steps

To a stirred solution of 2-methyl-thiazole-5-carboxylic acid (286 mg, 2.0 mmol) in THF (14 mL) at −72° C. and under argon was added n-butyllithium (2.50 mL of a 1.6M solution in hexane, 4.0 mmol) dropwise. After 2 h, a solution of 3-butyl-4-chloromethyl-5-methyl-isoxazole (375 mg, 2.0 mmol) in THF (6 mL) was added dropwise. After 2.5 h the reaction mixture was quenched with 10% aqueous citric acid (10 mL) then warmed to room temperature. The reaction mixture was extracted with ethyl acetate then the combined extracts were dried, filtered and concentrated. The resultant oil was dissolved in methanol (15 mL) and ether (7 mL) then (trimethylsilyl)diazomethane (3 mL of a 2M solution in ether, 6.0 mmol) was added dropwise. After 30 min, further (trimethylsilyl)diazomethane (3 mL of a 2M solution in ether, 6.0 mmol) was added. After 15 h, the reaction mixture was quenched with acetic acid (3 drops) then was concentrated and purified by chromatography (silica, 0 to 75% ethyl acetate in heptane) to give the title compound (360 mg, 58%) was a light brown oil. MS: m/e=309.2 [M+H]+.

Provenance & Evidence