METHYL 5-BROMO-1,3-THIAZOLE-4-CARBOXYLATE 97 synthesis

Yield: 53%

Reaction Conditions:

with tert.-butylnitrite in N,N-dimethyl-formamide at 80;

Steps:

3.1
Methyl 2-amino-4-bromothiazole-4-carboxylate (1.0 eq, 100 mg, 0.42 mmol) was dissolved in anhydrous DMF (0.8 ml). The mixture was heated to 80⁰C under nitrogen atmosphere. To the hot mixture, a solution of fe?t-Butyl nitrite (1.2 eq, 60 ul, 0.50 mmol) in DMF (0.8 ml) was added dropwise. After a few minutes, absence of gas evolution indicated completion of the reaction. The mixture was cooled down and poured onto a prepacked silica gel column. Flash chromatography using hexanes, then AcOEt/hexanes (2:8), provided methyl 5-bromothiazole-4-carboxylate as a yellow solid (49 mg, 53% yield). LCMS (ES): 95% pure, m/z 222 [M]⁺, 224 [M+2]⁺.

References:

CYLENE PHARMACEUTICALS, INC. WO2008/28168, 2008, A2 Location in patent:Page/Page column 157