Hydrochloric Acid → 3-(5-Bromo-2-methylphenyl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

HRID 1841892Notes

Reaction equation

HRID 1841892 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:24])=[C:6]([CH2:8][C:9]([NH:11][C:12]2([C:20](OC)=[O:21])[CH2:17][CH2:16][C:15]([F:19])([F:18])[CH2:14][CH2:13]2)=[O:10])[CH:7]=1.CN(C)C(=O)C.CC(C)([O-])C.[K+].Cl>O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:24])=[C:6]([C:8]2[C:9](=[O:10])[NH:11][C:12]3([CH2:13][CH2:14][C:15]([F:19])([F:18])[CH2:16][CH2:17]3)[C:20]=2[OH:21])[CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31374Dimethylacetamide2×HCID 23665647Potassium tert-butoxideHCID 68282721Methyl 1-{[(5-bromo-2-methylphenyl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

Product 1

HCID 682831323-(5-Bromo-2-methylphenyl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

11.0 g (27.2 mmol) of the compound from Example 10A were initially charged in a solution of 22 ml of DMA (N,N-dimethylacetamide), a solution of 10 ml of DMA and 3.54 g (1.1 eq.) of potassium tert-butoxide was added dropwise at 20-30° C. and the mixture was stirred at 30° C. for a further 1 h. The mixture was poured into 200 ml of water and the mixture was adjusted to pH 2 using aqueous 1N hydrochloric acid, the resulting precipitate was filtered off with suction, washed with water and dried in a vacuum drying cabinet at 50° C. The product was suspended in hot methyl tert-butyl ether, n-hexane was added and the mixture was filtered off with suction and dried. This gave 11.0 g (97% of theory) of the title compound in a purity of 89%.

Workup

  1. filtrationthe resulting precipitate was filtered off with suction
  2. washwashed with water
  3. customdried in a vacuum
  4. customdrying cabinet at 50° C
  5. additionn-hexane was added
  6. filtrationthe mixture was filtered off with suction
  7. customdried

Sources & evidence

ORD record
ord-4552137fdcdd4f8f81479c01df3838c4
Source dataset
uspto-grants-2015_02
Patent number
US08946124B2

Reaction notes

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