Hydrochloric Acid → 3-(4'-Chloro-4-methylbiphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

HRID 1466459Notes

Reaction equation

HRID 1466459 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([CH2:21][C:22]([NH:24][C:25]3([C:33]([O:35]C)=O)[CH2:30][CH2:29][C:28]([F:32])([F:31])[CH2:27][CH2:26]3)=[O:23])[CH:15]=2)=[CH:10][CH:9]=1.Cl>CN(C)C(=O)C>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([C:21]3[C:22](=[O:23])[NH:24][C:25]4([CH2:30][CH2:29][C:28]([F:31])([F:32])[CH2:27][CH2:26]4)[C:33]=3[OH:35])[CH:15]=2)=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 68283315Methyl 1-{[(4'-chloro-4-methylbiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

Product 1

HCID 601684123-(4'-Chloro-4-methylbiphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
30 °C

Procedure

Under argon and at 20 to 30° C., 3.31 g (28.0 mmol) of potassium tert-butoxide in 10 ml of N,N-dimethylacetamide were added to 11.1 g (25.5 mmol) of the compound from Example 6A in 22 ml of N,N-dimethylacetamide. The reaction mixture was stirred at 30° C. for 3 h. The reaction mixture was then added to 250 ml of ice-water, 1N aqueous hydrogen chloride solution was added dropwise until a pH of 2 had been reached and the precipitate was filtered off with suction and washed with water. For further purification, the product was taken up in methylene chloride and extracted with 50 ml of 1N aqueous sodium hydroxide solution, the aqueous phase was acidified with aqueous 1 N hydrochloric acid, filtered off with suction, washed with water and, for purification, suspended in 25 ml of hot acetonitrile on an ultrasonic bath, filtered off with suction, washed and dried. This gave 5.70 g (55% of theory) of the title compound.

Workup

  1. additionwas added dropwise until a pH of 2
  2. filtrationthe precipitate was filtered off with suction
  3. washwashed with water
  4. customFor further purification
  5. extractionextracted with 50 ml of 1N aqueous sodium hydroxide solution
  6. filtrationfiltered off with suction
  7. washwashed with water and, for purification
  8. customsuspended in 25 ml of hot acetonitrile on an ultrasonic bath
  9. filtrationfiltered off with suction
  10. washwashed
  11. customdried

Sources & evidence

ORD record
ord-01bc6c0ec732401ab3ab663f5595d8d6
Source dataset
uspto-grants-2015_04
Patent number
US09000026B2

Reaction notes

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