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

HRID 1466458ノート

反応式

HRID 1466458 の反応式
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][C:9]=1[F:37].Cl>CN(C)C=O>[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][C:9]=1[F:37]

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 86707849Methyl 1-{[(4'-chloro-3'-fluoro-4-methylbiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

生成物 1

HCID 601490113-(4'-Chloro-3'-fluoro-4-methylbiphenyl-3-yl)-8,8-difluoro-4-hydroxy-1-azaspiro[4.5]dec-3-en-2-one

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Under nitrogen 2.23 g (19.9 mmol) of potassium tert-butoxide were added to 8.19 g (18.0 mmol) of the compound from Example 5A in 80 ml of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 15 minutes. The reaction mixture was then added to ice-water, 1N aqueous hydrogen chloride solution was added dropwise until a pH of 1-2 had been reached, the mixture was stirred for 30 minutes and filtered off with suction, the filter cake was washed with water and the precipitate was dried. For further purification, the product was dissolved in 1N aqueous sodium hydroxide solution, precipitated by acidification with aqueous 1 N hydrochloric acid, stirred for 30 minutes, washed with water, filtered off and dried. This gave 7.50 g (97% of theory) of the title compound.

後処理

  1. additionwas added dropwise until a pH of 1-2
  2. stirringthe mixture was stirred for 30 minutes
  3. filtrationfiltered off with suction
  4. washthe filter cake was washed with water
  5. customthe precipitate was dried
  6. customFor further purification
  7. dissolutionthe product was dissolved in 1N aqueous sodium hydroxide solution
  8. customprecipitated by acidification with aqueous 1 N hydrochloric acid
  9. stirringstirred for 30 minutes
  10. washwashed with water
  11. filtrationfiltered off
  12. customdried

出典と根拠

ORDレコード
ord-90ea17bb6e0a4decbfa30388d612669b
出典データセット
uspto-grants-2015_04
特許番号
US09000026B2

反応ノート

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