반응 #1929068

반응 방정식

potassium carbonate

sodium bicarbonate

compound

Methyl 1-amino-4,4-difluorocyclohexanecarboxylate hydrochloride

compound

(4′-Chloro-3′-fluoro-4-methylbiphenyl-3-yl)acetic acid

thionyl chloride

→

Methyl 1-{[(4′-chloro-3′-fluoro-4-methylbiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

용매

acetonitrile

Ethyl acetate

반응 조건

후처리

1. 1
   농축concentrated
2. 2
   workup.DISSOLUTIONThe residue was dissolved in 30 ml of acetonitrile
3. 3
   기타The phases were separated
4. 4
   추출the aqueous phase was extracted repeatedly with ethyl acetate
5. 5
   건조the combined organic phases were dried over sodium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated
8. 8
   온도With ice-cooling
9. 9
   workup.STIRRINGthe mixture was stirred at room temperature overnight
10. 10
    추출extracted repeatedly with dichloromethane
11. 11
    세척the combined organic phases were washed repeatedly with 1N aqueous hydrogen chloride solution and saturated aqueous sodium bicarbonate solution
12. 12
    건조dried over sodium sulfate
13. 13
    여과filtered
14. 14
    농축concentrated
15. 15
    기타This gave 8.22 g (83% of theory) of the title compound, which were converted without further purification

실험 절차

6.06 g (21.7 mmol) of the compound from Example 1A were dissolved in 7.5 ml (103 mmol) of thionyl chloride. The reaction mixture was stirred at 80° C. for 1 h and then concentrated. The residue was dissolved in 30 ml of acetonitrile. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added to 5.00 g (21.8 mmol) of the compound from Example 4A. The phases were separated, the aqueous phase was extracted repeatedly with ethyl acetate and the combined organic phases were dried over sodium sulfate, filtered and concentrated. 140 ml of acetonitrile and 8.76 g (63.4 mmol) of potassium carbonate were added to the residue. With ice-cooling, the solution of the acid chloride was added dropwise, and the mixture was stirred at room temperature overnight. The mixture was then added to ice-water and extracted repeatedly with dichloromethane, and the combined organic phases were washed repeatedly with 1N aqueous hydrogen chloride solution and saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated. This gave 8.22 g (83% of theory) of the title compound, which were converted without further purification.

출처