Hydrochloric Acid → Methyl 3-oxo-5-(1,3-thiazole-2-yl)-4-pentenoate

Methyl 3-oxo-5-(1,3-thiazole-2-yl)-4-pentenoate was prepared from 3-(1,3-thazol-2-yl)-2-propenoic acid (Bull. Chem. Soc. Jap. 1974, 47, 151.) according to the literature procedure (Heterocycles 1994, 38, 751.). To a stirred solution of 3-(1,3-thiazol-2-yl)-2-propenoic acid (100.0 g, 644.4 mmol) in DMF (1000 ml) was added 1,1′-carbonyldiimidazole (115.0 g, 708.9 mmol) in small portions. After stirring at room temperature for 5 hours, to the reaction mixture were added anhydrous magnesium chloride (73.6 g, 773.0 mmol) and monomethyl malonate potassium salt (120.8 g, 773.0 mmol). The resulting suspension was heated at 55° C. with stirring for 14 h. After cooling to room temperature, the reaction mixture was poured into 1500 ml of 2 N HCl, and extracted with a mixture of EtOAc (1500 ml) and toluene (500 ml). The organic phase was separated and the aqueous phase was extracted with a 3:1 mixture of EtOAc and toluene (2000 ml). The combined organic phase was washed with H2O (1000 ml) and brine (1000 ml), dried (Na2SO4) and evaporated to afford 132.0 g of methyl 3-oxo-5-(1,3-thiazole-2-yl)-4-pentenoate (1/2 of keto/enol form)

1. temperatureThe resulting suspension was heated at 55° C.
2. stirringwith stirring for 14 h
3. temperatureAfter cooling to room temperature
4. extractionextracted with a mixture of EtOAc (1500 ml) and toluene (500 ml)
5. customThe organic phase was separated
6. extractionthe aqueous phase was extracted with a 3:1 mixture of EtOAc and toluene (2000 ml)
7. washThe combined organic phase was washed with H2O (1000 ml) and brine (1000 ml)
8. dry with materialdried (Na2SO4)
9. customevaporated

ORD record

ord-bd9aa905e94843dd9c7efc9a6b905ed6

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06444677B2