N-METHOXY-N-METHYL-THIAZOLE-2-CARBOXAMIDE synthesis

Yield:885278-18-2 70%

Reaction Conditions:

Stage #1: 1,3-thiazole-2-carboxylic acidwith 2-chloro-4,6-dimethoxy-1 ,3,5-triazine in tetrahydrofuran at 0; for 0.25 h;
Stage #2: with 4-methyl-morpholine in tetrahydrofuran at 20; for 1.5 h;
Stage #3: N,O-dimethylhydroxylamine*hydrochloride in tetrahydrofuran at 0 - 20;

Steps:

1.1

Thiazole-2-carboxylic acid (5 g, 38.7 mmol) and CDMT (7.47 g, 42.6 mmol) were suspended in THF under N₂ at O⁰C. After 15 min NMM (11.7 g, 12.76 mL, 116 mmol) was added dropwise. The reaction mixture was stirred for 1.5 hr at RT, and then N- methoxymethanamine hydrochloride was added at 0 ⁰C. The reaction mixture was stirred over night at room temperature and was then concentrated under reduced pressure. The residue was redissolved in ethyl acetate and the solution was washed with water and brine, dried over anhydrous sodium sulfate. The residue after evaporation of solvents was purified by column chromatography eluting with 30% EtOAc/hexanes to give 4.6 g (70%) of the desired product as pale yellow oil.

References:

WO2009/5460,2009,A1 Location in patent:Page/Page column 21-22