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

HRID 504324노트

반응식

HRID 504324 반응식
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]

참가 물질

8

반응물 4

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 162279661-(4-Bromophenyl)cyclopropane-1-carboxylic acidHCID 178418339ButyllithiumHCID 178448196HCID 178448196, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매2회HCID 8058Hexane용매HCID 8900Heptane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2ab07697b76047d282718a58f530d26b
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07776874B2

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