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

HRID 1466462Notes

Reaction equation

HRID 1466462 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([CH2:15][C:16]([NH:18][C:19]3([C:27]([O:29]C)=O)[CH2:24][CH2:23][C:22]([F:26])([F:25])[CH2:21][CH2:20]3)=[O:17])[C:9]=2[CH3:31])=[CH:4][CH:3]=1.CN(C)C(=O)C.CC(C)([O-])C.[K+].Cl>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([C:15]3[C:16](=[O:17])[NH:18][C:19]4([CH2:20][CH2:21][C:22]([F:26])([F:25])[CH2:23][CH2:24]4)[C:27]=3[OH:29])[C:9]=2[CH3:31])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31374Dimethylacetamide2×HCID 23665647Potassium tert-butoxideHCID 68283283Methyl 1-{[(4'-chloro-2,4-dimethylbiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

Product 1

HCID 601683333-(4'-Chloro-2,4-dimethylbiphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2.55 g (5.29 mmol) of the compound from Example 9A were initially charged in a solution of 5 ml of DMA (N,N-dimethylacetamide), a solution of 5 ml of DMA and 1.88 g (3 eq.) of potassium tert-butoxide was added dropwise at 20° C. and the mixture was stirred at room temperature for 24 h. The mixture was poured into 200 ml of water and the reaction was adjusted to pH 2 using concentrated aqueous hydrochloric acid, and the resulting residue was filtered off with suction. Purification by flash column chromatography (silica gel; ethyl acetate/n-hexane 2:1) gave 0.87 g (31% of theory) of the title compound.

Workup

  1. filtrationthe resulting residue was filtered off with suction
  2. customPurification by flash column chromatography (silica gel; ethyl acetate/n-hexane 2:1)

Sources & evidence

ORD record
ord-2e0b6d3337d3444b9aac830107b82836
Source dataset
uspto-grants-2015_04
Patent number
US09000026B2

Reaction notes

Loading…