2-Bromopyridine → 3-Hydroxy-3-pyridin-2-yl-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

HRID 2202790노트

반응식

HRID 2202790 반응식
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[C:13]([O:17][C:18]([N:20]1[CH:25]2[CH2:26][CH2:27][CH:21]1[CH2:22][C:23](=[O:28])[CH2:24]2)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(=O)([O-])O.[Na+]>C1COCC1.C(OCC)(=O)C>[C:13]([O:17][C:18]([N:20]1[CH:25]2[CH2:26][CH2:27][CH:21]1[CH2:22][C:23]([OH:28])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)[CH2:24]2)=[O:19])([CH3:16])([CH3:14])[CH3:15]

참가 물질

7

반응물 4

HCID 79732-BromopyridineHCID 516892Sodium BicarbonateHCID 2794767tert-Butyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 674646933-Hydroxy-3-pyridin-2-yl-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester수율 35.2%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

n-Butyl lithium (2.5 M, 2.4 mL, 6.0 mmol) was added dropwise to a solution of 2-bromopyridine (0.57 mL, 6.0 mmol) in THF (10 mL) at −78° C. under nitrogen and stirred for 30 minutes. A solution of 3-oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (1.3 g, 5.78 mmol) in THF (10 mL) was added dropwise and the mixture stirred at −78° C. for 1 hour. The reaction mixture was warmed to room temperature then saturated aqueous sodium hydrogen carbonate and ethyl acetate were added, the organics separated, dried over magnesium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was purified by flash chromatography on silica eluting with 20-50% ethyl acetate/pentane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.62 g). LCMS m/z 305.3 [M+H]+. R.T.=2.50 min (Analytical Method 3).

후처리

  1. stirringthe mixture stirred at −78° C. for 1 hour
  2. dry with materialthe organics separated, dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent removed by evaporation under vacuum
  5. customThe residue was purified by flash chromatography on silica eluting with 20-50% ethyl acetate/pentane
  6. additionThe fractions containing the desired product
  7. concentrationwere concentrated under vacuum

출처 및 근거

ORD 기록
ord-db04769303414bd09a69fae50481e1f8
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365564B2

반응 노트

불러오는 중…