tert-Butyl 4-oxopiperidine-1-carboxylate → 1-(4-[1-(Tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl]phenyl}cyclopropanecarboxylic acid

HRID 504324ノート

反応式

HRID 504324 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=[O:12])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([Mg]CCCC)CCC.C([Li])CCC.[O:28]=[C:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]1>CCCCCCC.CCCCCC.C1COCC1>[C:38]([O:37][C:35]([N:32]1[CH2:33][CH2:34][C:29]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3([C:11]([OH:13])=[O:12])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)([OH:28])[CH2:30][CH2:31]1)=[O:36])([CH3:41])([CH3:39])[CH3:40]

参加物

8

反応物 4

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 162279661-(4-Bromophenyl)cyclopropane-1-carboxylic acidHCID 178418339ButyllithiumHCID 178448196HCID 178448196、化合物

生成物 1

HCID 666615921-(4-[1-(Tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl]phenyl}cyclopropanecarboxylic acid

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒HCID 8900Heptane溶媒

実験手順

A solution of 1-(4-bromophenyl)cyclopropanecarboxylic acid (1000.0 mg, 0.0041480 mol) in tetrahydrofuran (30 mL, 0.4 mol) was cooled below −20° C. under a N2 atmosphere and dibutylmagnesium in heptane (1.0 M, 2.2 mL) was slowly added to the solution while the reaction temperature was maintained below −20° C. Then 2.5 M of n-butyllithium in hexane (1.8 mL) was slowly added to the mixture below −20° C. under effective stirring. After stirring below −20° C. for 1 h, a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (0.909 g, 0.00456 mol) in THF (20.0 mL) was added to the mixture below −20° C. After stirring below −20° C. for 1 h, the reaction was quenched with ammonium chloride. The product was extracted with EtOAc and the combined extract was washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated and then purified by Combiflash, eluting with 5% methanol in methylene chloride.

後処理

  1. temperaturewas maintained below −20° C
  2. stirringAfter stirring below −20° C. for 1 h
  3. customthe reaction was quenched with ammonium chloride
  4. extractionThe product was extracted with EtOAc
  5. extractionthe combined extract
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated
  10. custompurified by Combiflash
  11. washeluting with 5% methanol in methylene chloride

出典と根拠

ORDレコード
ord-2ab07697b76047d282718a58f530d26b
出典データセット
uspto-grants-2010_08
特許番号
US07776874B2

反応ノート

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