Reaction #1929079

Reaction equation

potassium tert-butoxide

compound

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

hydrogen chloride

→

3-(4′-Chloro-3′-fluoro-4-methylbiphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise until a pH of 1-2
2. 2
   workup.STIRRINGthe mixture was stirred for 30 minutes
3. 3
   Filtrationfiltered off with suction
4. 4
   Washthe filter cake was washed with water
5. 5
   Otherthe precipitate was dried
6. 6
   OtherFor further purification
7. 7
   workup.DISSOLUTIONthe product was dissolved in 1N aqueous sodium hydroxide solution
8. 8
   Otherprecipitated by acidification with aqueous 1 N hydrochloric acid
9. 9
   workup.STIRRINGstirred for 30 minutes
10. 10
    Washwashed with water
11. 11
    Filtrationfiltered off
12. 12
    Otherdried

Procedure

Under nitrogen, 2.23 g (19.9 mmol) of potassium tert-butoxide were added to 8.19 g (18.0 mmol) of the compound from Example 5A in 80 ml of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 15 minutes. The reaction mixture was then added to ice-water, 1N aqueous hydrogen chloride solution was added dropwise until a pH of 1-2 had been reached, the mixture was stirred for 30 minutes and filtered off with suction, the filter cake was washed with water and the precipitate was dried. For further purification, the product was dissolved in 1N aqueous sodium hydroxide solution, precipitated by acidification with aqueous 1 N hydrochloric acid, stirred for 30 minutes, washed with water, filtered off and dried. This gave 7.50 g (97% of theory) of the title compound.

Source