Methanamine, N-methoxy-, hydrochloride (1:1) → 4-Methoxymethyl-2-phenyl-thiazole-5-carboxylic Acid Methoxy-methyl Amide

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Reaction Conditions

Reaction Steps

A solution of N,O-dimethylhydroxylamine hydrochloride(13.3 g, 136.3 mmole, 6.0 eq) in dry CH2Cl2(250 ml) at 0° C. was treated dropwise with neat dimethylaluminum chloride (12.7 ml, 136.3 mmole, 6.0 eq) and the resulting mixture stirred at 0° C. for 2 hours then allowed to warm to RT. To this mixture was added dropwise a solution of the above-prepared 4-methoxymethyl-2-phenyl-thiazole-5-carboxylic acid methyl ester (5.98 g, 22.71 mmole, 1.0 eq) in CH2Cl2 (20 ml). The yellow mixture was then stirred at room temperature under nitrogen for one hour and re-cooled to 0° C. The mixture was quenched slowly by adding 2.0N NaOH dropwise, warmed to room temperature, and extracted with two portions of CH2Cl2. The organic phase was washed successively with 1.0N NaOH and brine, dried over MgSO4, and concentrated in vacuo to give a yellow oil. Silica gel chromatography eluting with (4:1) hexanes-ethyl acetate to give 6.5 g (97%) of the title compound as a yellow waxy crystalline solid. 1H NMR (CDCl3): δ 3.35 (s, 3H), 3.5 (s, 3H), 3.7 (s, 3H), 4.95 (s, 2H), 7.4-7.5 (m, 3H), 8.0 (m, 2H).

Provenance & Evidence