Dimethyl-1,3-thiazole-5-carboxylic acid → HCID 66643863, compound

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Reaction Steps

To a stirred solution of 2,4-dimethyl-thiazole-5-carboxylic acid (0.84 g, 5.34 mmol) in THF (50 mL) at −78° C. and under argon was added n-butyllithium (7.63 mL of a 1.40M solution in hexane, 10.7 mmol) dropwise. After 1 h, a solution of 5-methyl-3-phenyl-isoxazole-4-carbaldehyde (1.0 g, 5.34 mmol) in THF (50 mL) was added dropwise. After 3 h the reaction mixture was quenched with 10% aqueous citric acid (50 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 redissolved in ethyl acetate, washed with water then dried, filtered and concentrated in vacuo. The resultant residue was dissolved in methanol (40 mL) and ether (20 mL) then (trimethylsilyl)diazomethane (4.0 mL of a 2M solution in ether, 8.0 mmol) was added dropwise. After 30 min, further (trimethylsilyl)diazomethane (4.0 mL of a 2M solution in ether, 8.0 mmol) was added. After 15 h, the reaction mixture was quenched with acetic acid (3 drops) then was concentrated and the residue redissolved in ethyl acetate and washed with NaOH (2 N). The organic phase was dried, filtered and concentrated then purified by chromatography (silica, 10 to 40% ethyl acetate in heptane) to give the title compound (500 mg, 26%) as a yellow foam. MS: m/e=359.0 [M]+.

Provenance & Evidence