Diisopropylamine → 6'-Fluorospiro[1-azabicyclo[2.2.2]octane-3,2'(3'h)-furo[2,3-b]pyridine]

HRID 48529

반응식

HRID 48529 반응식
[C:1]1([Li])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:8]([NH:11][CH:12]([CH3:14])C)(C)C.[C:15](=[O:17])=O.CC(C)=O.[F:22][C:23]1[CH:28]=[CH:27]C=C(F)[N:24]=1.C(=O)(O)[O-].[Na+].[H-].[Na+]>O1CCCC1.CN(C=O)C>[F:22][C:23]1[N:24]=[C:15]2[O:17][C:5]3([CH:4]4[CH2:3][CH2:2][N:11]([CH2:12][CH2:14]4)[CH2:8]3)[CH2:6][C:1]2=[CH:27][CH:28]=1

참가 물질

9

반응물 6

HCID 7912DiisopropylamineHCID 24758Sodium hydrideHCID 739342,6-DifluoropyridineHCID 516892Sodium Bicarbonate2회HCID 18522661Acetone cardiceHCID 178506676HCID 178506676, 화합물

생성물 1

HCID 159082486'-Fluorospiro[1-azabicyclo[2.2.2]octane-3,2'(3'h)-furo[2,3-b]pyridine]수율 8%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

A solution of phenyllithium (1.8 M in cyclohexane, 13.5 mL) was added to THF (15 mL) under argon. Diisopropylamine (0.5 mL) was added, and the solution was cooled to −78° C. (dry ice/acetone bath temperature). To the resulting solution, 2,6-difluoropyridine (1.23 mL, 1.56 g, 13.6 mmol) was added dropwise, then after 1 h, a solution of spiro[1-azabicyclo[2.2.2]octane-3,2′-oxirane] N-borane complex (765 mg, 5.0 mmol) in tetrahydrofuran was added dropwise. The solution was stirred at −78° C. for 1 h and the cooling bath was then replaced with a dry ice/acetonitrile bath. The solution was then stirred overnight, warming to room temperature. Saturated aqueous sodium bicarbonate was added, and the solution was then extracted with chloroform. The extract was then dried (MgSO4), filtered, and evaporated. The residue was dissolved in DMF (20 mL), and was then added to a suspension of hexane-washed sodium hydride (60% mixture with mineral oil, 507 mg, 12.7 mmol) in DMF (20 mL) stirred at 0° C. The solution was stirred overnight, warming to room temperature. Saturated aqueous sodium bicarbonate was added to the solution, which was then extracted with chloroform. The extract was then dried (MgSO4), filtered, and evaporated, and the residue was purified by HPLC using a gradient of 5-50% ethyl acetate and hexane to give the sub-title compound (102 mg, 8%, 0.41 mmol): electrospray MS (m/z) 247 [M−H]+.

후처리

  1. customthe cooling bath was then replaced with a dry ice/acetonitrile bath
  2. stirringThe solution was then stirred overnight
  3. temperaturewarming to room temperature
  4. extractionthe solution was then extracted with chloroform
  5. dry with materialThe extract was then dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in DMF (20 mL)
  9. additionwas then added to a suspension of hexane-
  10. stirringstirred at 0° C
  11. stirringThe solution was stirred overnight
  12. temperaturewarming to room temperature
  13. extractionwas then extracted with chloroform
  14. dry with materialThe extract was then dried (MgSO4)
  15. filtrationfiltered
  16. customevaporated
  17. customthe residue was purified by HPLC

출처 및 근거

ORD 기록
ord-ef34ca03816647bcb9908d540df736cf
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06703502B2

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