Sodium Hydroxide → 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylic acid

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Reaction Steps

A solution of methyl 5-ethyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (300 mg, 1.2 mmol) [Prepared in Example 98] and N-bromosuccinimide (213 mg, 1.2 mmol) in Tetrahydrofuran (5.99 ml) was stirred in a sealed tube for 1 h at 70° C. Aqueous sodium hydroxide (4.0 ml, 23.97 mmol) was added in one portion and the solution stirred an additional 1 h. The reaction mixture was then partitioned between H2O-DCM and the pH of the aqueous phase was adjusted to ˜4 and washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated then purified via column chromatography (silica, 20% EtOAC in hexanes) yielding 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylic acid (378 mg, 1.2 mmol, 100% yield) as a yellow oil: LCMS (ES) m/e 314, 316 (M, M+2)+.

Provenance & Evidence