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

HRID 1466460Notes

Reaction equation

HRID 1466460 reaction equation
[F:1][C:2]1([F:30])[CH2:7][CH2:6][C:5]([NH:12][C:13](=[O:29])[CH2:14][C:15]2[CH:16]=[C:17]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH:18]=[CH:19][C:20]=2[CH3:21])([C:8](OC)=[O:9])[CH2:4][CH2:3]1.CN(C)C(=O)C.CC(C)([O-])C.[K+].Cl>O>[F:30][C:2]1([F:1])[CH2:7][CH2:6][C:5]2([NH:12][C:13](=[O:29])[C:14]([C:15]3[CH:16]=[C:17]([C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=4)[CH:18]=[CH:19][C:20]=3[CH3:21])=[C:8]2[OH:9])[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31374Dimethylacetamide2×HCID 23665647Potassium tert-butoxideHCID 68283296Methyl 4,4-difluoro-1-{[(4'-fluoro-4-methylbiphenyl-3-yl)acetyl]amino}cyclohexanecarboxylate

Product 1

HCID 601684118,8-Difluoro-3-(4'-fluoro-4-methylbiphenyl-3-yl)-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2.80 g (5.94 mmol) of the compound from Example 7A were initially charged in a solution of 8 ml of DMA (N,N-dimethylacetamide), a solution of 5 ml of DMA and 1.75 g (2.5 eq.) of potassium tert-butoxide was added dropwise at 20° C. and the mixture was stirred at room temperature for 4 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 1:1) gave 1.07 g (44% 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 1:1)

Sources & evidence

ORD record
ord-2a2cd56a1ee74536bf2755dfe93a2203
Source dataset
uspto-grants-2015_04
Patent number
US09000026B2

Reaction notes

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