Sodium hydride → tert-Butyl 4-cyano-4-(2,4-difluorophenyl)piperidine-1-carboxylate

HRID 1066994ノート

反応式

HRID 1066994 の反応式
[C:1]([O:5][C:6](=[O:14])[N:7]([CH2:11][CH2:12]Cl)[CH2:8][CH2:9]Cl)([CH3:4])([CH3:3])[CH3:2].[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[CH2:23][C:24]#[N:25].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:7]1[CH2:11][CH2:12][C:23]([C:24]#[N:25])([C:17]2[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=2[F:15])[CH2:9][CH2:8]1)=[O:14])([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 695652,4-DifluorophenylacetonitrileHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

生成物 1

HCID 18353388tert-Butyl 4-cyano-4-(2,4-difluorophenyl)piperidine-1-carboxylate収率 62%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To bis(2-chloroethyl)-carbamic acid tert-butyl ester (1.0 g, 3.8 mmol) and 2,4-difluorophenyl acetonitrile (0.581 g, 3.8 mmol) in DMF (35 ml), NaH (95%) (0.258 g, 9.68 mmol) was added in one batch at 0° C. The solution was stirred for 10 minutes at room temperature. When foaming subsided, the solution was heated at 60° C. for 24 hours. It was then quenched with water at 0° C. and concentrated. The residue was extracted with ethyl acetate (25 mL) and washed three times with water (15 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (hexane:ethyl acetate 4:1) yielded 0.720 g (62%) of the product as a syrup.

後処理

  1. temperaturethe solution was heated at 60° C. for 24 hours
  2. customIt was then quenched with water at 0° C.
  3. concentrationconcentrated
  4. extractionThe residue was extracted with ethyl acetate (25 mL)
  5. washwashed three times with water (15 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by column chromatography (hexane:ethyl acetate 4:1)

出典と根拠

ORDレコード
ord-403552535ca44a3ba159249b6d8cbad5
出典データセット
uspto-grants-2001_06
特許番号
US06245773B1

反応ノート

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