1-Bromo-4-fluorobenzene → 8-Benzyl-3-(4-fluoro-phenyl)-8-aza-bicyclo[3.2.1]octan-3-ol

HRID 72834

반응식

HRID 72834 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.C([Li])CCC.[CH2:14]([N:21]1[CH:26]2[CH2:27][CH2:28][CH:22]1[CH2:23][C:24](=[O:29])[CH2:25]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[OH-].[Na+]>C(OCC)C>[CH2:14]([N:21]1[CH:22]2[CH2:28][CH2:27][CH:26]1[CH2:25][C:24]([C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1)([OH:29])[CH2:23]2)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

참가 물질

6

반응물 4

HCID 99931-Bromo-4-fluorobenzeneHCID 14798Sodium HydroxideHCID 1198468-Benzyl-8-azabicyclo(3.2.1)octan-3-oneHCID 178418339Butyllithium

생성물 1

HCID 130912278-Benzyl-3-(4-fluoro-phenyl)-8-aza-bicyclo[3.2.1]octan-3-ol

시약·촉매·용매 1

HCID 3283Diethyl Ether용매3회

반응 조건

온도
-35 °C

실험 절차

1-Bromo-4-fluoro-benzene (22.7 g) dissolved in diethylether (100 mL) is added to a solution of n-butyllithium (1.7 mol/L in pentane, 86.8 mL) in diethylether (200 mL) cooled to −35° C. The combined solutions are stirred at −35 to −40° C. for 1 h, before 8-benzyl-8-aza-bicyclo[3.2.1]octan-3-one (22.5 g) dissolved in diethylether (150 mL) is added quickly. The solution is warmed to −10° C. within 1 h and then the reaction is quenched by the addition of aqueous NH4Cl solution. The resulting mixture is extracted with ethyl acetate, the combined extracts are washed with brine, and 4 M hydrochloric acid is added to the organic phase. The organic phase is separated from the aqueous phase and an oily precipitation formed after the addition. The oily and aqueous phase are combined and basified with 4 M aqueous NaOH solution and the resulting mixture is extracted with ethyl acetate. The organic extracts are dried (Na2SO4) and the solvent is evaporated to give the title compound.

후처리

  1. additionis added quickly
  2. temperatureThe solution is warmed to −10° C. within 1 h
  3. customthe reaction is quenched by the addition of aqueous NH4Cl solution
  4. extractionThe resulting mixture is extracted with ethyl acetate
  5. washthe combined extracts are washed with brine, and 4 M hydrochloric acid
  6. additionis added to the organic phase
  7. customThe organic phase is separated from the aqueous phase
  8. customan oily precipitation
  9. customformed
  10. additionafter the addition
  11. extractionthe resulting mixture is extracted with ethyl acetate
  12. dry with materialThe organic extracts are dried (Na2SO4)
  13. customthe solvent is evaporated

출처 및 근거

ORD 기록
ord-3daac1c55a1b46dd80d595152ab04052
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829027B2

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