5-Thiazolepropanoic acid, 2-bromo-, methyl ester synthesis

Yield: 36%

Reaction Conditions:

with tert.-butylnitrite;copper(I) bromide in acetonitrile at 50; for 1 h;

Steps:

B INTERMEDIATE 7 METHYL 3 -(2-ETHYNYL- 1 ,3 -THIAZOL-5 -YL)PROPANOATE
Step B. Methyl 3-(2-bromo-l,3-thiazol-5-yl)propanoate To a mixture of methyl 3-(2-amino-l,3-thiazol-5-yl)propanoate (2.6 g, 9.25 mmol) and CuBr (1.33 g, 9.25 mmol) in acetonitrile (40 ml) at 50 °C was added tert-butyl nitrite (1.43 ml, 12.02 mmol) slowly. After 1 h, the reaction mixture was cooled to room temperature and partitioned between EtOAc and saturated aqueous NH₄C1. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (0 - 50% EtOAc/hexanes) to give methyl 3-(2-bromo-l,3-thiazol-5- yl)propanoate (850 mg, 36%). MS (ES⁺) m/z: 249.87 (M+H)⁺, 251.85 (M+H+2)⁺.

References:

MERCK SHARP & DOHME CORP.;LIN, Songnian;CAMPBELL, Brian;DEWNANI, Sunita, V.;KATS-KAGAN, Roman;PARMEE, Emma, R.;XU, Jiayi;XU, Libo;ZHANG, Rui WO2014/99578, 2014, A1 Location in patent:Page/Page column 48