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

HRID 1841900Notes

Reaction equation

HRID 1841900 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[CH2:15][C:16]([NH:18][C:19]1([C:27]([O:29]C)=O)[CH2:24][CH2:23][C:22]([F:26])([F:25])[CH2:21][CH2:20]1)=[O:17].CN(C)C(=O)C.CC(C)([O-])C.[K+].[ClH:43]>O>[Cl:43][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([Cl:14])=[CH:12][CH:13]=2)=[CH:4][C:3]=1[C:15]1[C:16](=[O:17])[NH:18][C:19]2([CH2:20][CH2:21][C:22]([F:25])([F:26])[CH2:23][CH2:24]2)[C:27]=1[OH:29]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31374Dimethylacetamide2×HCID 23665647Potassium tert-butoxideHCID 86707850Methyl 1-{[(4,4'-dichlorobiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

Product 1

HCID 601684103-(4,4'-Dichlorobiphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3.20 g (5.74 mmol) of the compound from Example 8A were initially charged in a solution of 14 ml of DMA (N,N-dimethylacetamide), a solution of 9 ml of DMA and 1.69 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 1.50 g (52% of theory) of the title compound of melting point m.p. 156° C.

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-0b226b9005804d24a12c0a54af2801a8
Source dataset
uspto-grants-2015_02
Patent number
US08946124B2

Reaction notes

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