Hydrochloric Acid → HCID 117600729, compound

Temperature

-78 °C

To a suspension of NaH (60%, 1.77 g, 44.2 mmol) in dry THF (30 mL) was added ethyl 2-(diethoxyphosphoryl)acetate (10.12 g, 44.2 mmol) at −78° C. After being stirred at −78° C. for 1 hour, a solution of 14 g (44.2 mmol) (3-Bromo-5-chloro-phenyl)-(5-methyl-thiazol-2-yl)-methanone in THF (10 mL) was added drop wise over 30 min. The mixture was stirred at −78° C. for 30 min and then warmed to room temperature with stirring overnight. The mixture was cooled to 0° C. and treated with water (50 mL), pH value was adjusted to 6 with HCl (0.5N) and extracted with EA (50 mL×3). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with petroleum ether/EtOAc mixtures to afford (Z)-3-(3-Bromo-5-chloro-phenyl)-3-(5-methyl-thiazol-2-yl)-acrylic acid ethyl ester as an gel (18 g, yield=106%) The material is used without further purification in the next step.

1. stirringThe mixture was stirred at −78° C. for 30 min
2. temperaturewarmed to room temperature
3. stirringwith stirring overnight
4. temperatureThe mixture was cooled to 0° C.
5. extractionextracted with EA (50 mL×3)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel chromatography
10. washeluting with petroleum ether/EtOAc

ORD record

ord-8ef4a44bb4ae4bb8b3ecc77e98146682

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150526B2