beta-Chloroethyl acetate → 2-Chloro-3-[2-methyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)-5-oxazolyl]propionic acid

To a solution of [2-methyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)-5-oxazolyl]methanol (3.3 g) in (40 mL) was added thionyl chloride (1.5 mL) at 0° C. After stirring at room temperature for 15 min, the reaction mixture was concentrated. To the residue was added saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give an oil. To a mixed solution of 2-chloroethyl acetate (2.68 g) and N,N-dimethylformamide (40 mL) was added sodium hydride (60% in oil, 0.6 g) and the mixture was stirred at 0° C. for 5 min. To this the reaction mixture was added a solution of the aforementioned oil in N,N-dimethylformamide (10 mL) at room temperature and the mixture was stirred at room temperature for 2.5 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was diluted with ethanol (30 mL) and a 2N aqueous sodium hydroxide solution (16 mL) was added at 0° C. and the mixture was stirred for 20 min. Water was added to the reaction mixture and the mixture was washed with diethyl ether. The aqueous layer was acidified with 2N aqueous hydrochloric acid solution, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The precipitated crystals were collected by filtration and recrystallized from ethanol to give 2-chloro-3-[2-methyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)-5-oxazolyl]propionic acid (3.93 g, yield 91%) as colorless prism crystals. melting point: 141–142° C.

1. concentrationthe reaction mixture was concentrated
2. additionTo the residue was added saturated aqueous sodium hydrogen carbonate
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed successively with water and saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated
7. customto give an oil
8. stirringthe mixture was stirred at 0° C. for 5 min
9. stirringthe mixture was stirred at room temperature for 2.5 hrs
10. extractionthe mixture was extracted with ethyl acetate
11. washThe organic layer was washed successively with water and saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated
14. additionThe residue was diluted with ethanol (30 mL)
15. additiona 2N aqueous sodium hydroxide solution (16 mL) was added at 0° C.
16. stirringthe mixture was stirred for 20 min
17. additionWater was added to the reaction mixture
18. washthe mixture was washed with diethyl ether
19. extractionthe mixture was extracted with ethyl acetate
20. washThe organic layer was washed successively with water and saturated brine
21. dry with materialdried over anhydrous magnesium sulfate
22. concentrationconcentrated
23. filtrationThe precipitated crystals were collected by filtration
24. customrecrystallized from ethanol

ORDレコード

ord-5daf3ac398f04aba868461147afacfca

出典データセット

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07183276B2