Hydrochloric Acid → 3-[4-(4-Chlorophenyl)-2-phenyl-5-thiazolyl]propionic acid

温度

0 °C

To a solution of ethyl malonate (17.5 g) in N,N-dimethylformamide (50 mL) was added sodium hydride (4.38 g) and the mixture was stirred at 0° C. for 30 min, after which a solution of 5-(bromomethyl)-4-(4-chlorophenyl)-2-phenylthiazole (8.0 g) in N,N-dimethylformamide (200 mL) was added at 0° C. The mixture was stirred at 0° C. for 2 hrs. and poured into dilute hydrochloric acid. The mixture was extracted with ethyl acetate and the organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated to give a yellow oil. This oil was dissolved in ethanol (140 mL) and 10% aqueous sodium hydroxide solution (140 mL) was added. The mixture was stirred at 60° C. for 2 hrs. and the reaction mixture was poured into water. The mixture was washed with diethyl ether and the aqueous layer was acidified with dilute hydrochloric acid. The mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give a yellow powder. This powder was dissolved in pyridine (140 mL) and the mixture was stirred at 100° C. for 2 hrs. The reaction mixture was concentrated and diluted with dilute hydrochloric acid. The mixture was extracted with ethyl acetate, and the organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated to give 3-[4-(4-chlorophenyl)-2-phenyl-5-thiazolyl]propionic acid (5.71 g, 75%) as a yellow powder. Recrystallization from ethyl acetate-hexane gave colorless prism crystals, melting point: 142–143° C.

1. stirringThe mixture was stirred at 0° C. for 2 hrs
2. extractionThe mixture was extracted with ethyl acetate
3. washthe organic layer was washed with water
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated
6. customto give a yellow oil
7. stirringThe mixture was stirred at 60° C. for 2 hrs
8. washThe mixture was washed with diethyl ether
9. extractionThe mixture was extracted with ethyl acetate
10. washthe organic layer was washed with saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated
13. customto give a yellow powder
14. stirringthe mixture was stirred at 100° C. for 2 hrs
15. concentrationThe reaction mixture was concentrated
16. additiondiluted with dilute hydrochloric acid
17. extractionThe mixture was extracted with ethyl acetate
18. washthe organic layer was washed with water
19. dry with materialdried over anhydrous magnesium sulfate
20. concentrationconcentrated

ORDレコード

ord-d5289a44ed654aafb48bb144c3e64add

出典データセット

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07183276B2