Diisopropylethylamine → (S)-tert-butyl 5,5-difluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate

HRID 1920170노트

반응식

HRID 1920170 반응식
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][N:13]([C:15]([O-])=O)[CH2:12][C:11]([F:19])([F:18])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.ClC1[CH:35]=[CH:34][N:33]=[CH:32][C:31]=1[N+:36]([O-:38])=[O:37]>CO.CCOC(C)=O.[Pd]>[F:18][C:11]1([F:19])[CH2:12][N:13]([C:15]2[CH:35]=[CH:34][N:33]=[CH:32][C:31]=2[N+:36]([O-:38])=[O:37])[CH2:14][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10]1

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 27357814-Chloro-3-nitropyridineHCID 866447355-(Tert-butoxycarbonylamino)-3,3-difluoropiperidine-1-carboxylate

생성물 1

HCID 67501048(S)-tert-butyl 5,5-difluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate수율 19%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 887Methanol용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 5-(tert-butoxycarbonylamino)-3,3-difluoropiperidine-1-carboxylate (1 eq) in 5 mL of methanol and 5 mL of EtOAc was added 10% Pd/C (0.1 eq). The resulting suspension was stirred at H2 atmosphere overnight. The crude solids were filtered through a pad of Celite on a paper lined Buchner funnel, washed with MeOH, then concentrated in vacuo. The residue was dissolved in 5 mL of isopropanol and DIPEA (2.0 eq) and 4-chloro-3-nitropyridine (1.5 eq) were added. The reaction mixture was stirred at 70° C. for 3 hours, at which point the reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was diluted with 120 mL of EtOAc, washed with brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (5% methanol in EtOAc:hexanes=1:1) to yield (S)-tert-butyl 5,5-difluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate (19%). LC/MS (m/z): 359.0 (MH+), Rt: 0.65 min.

후처리

  1. filtrationThe crude solids were filtered through a pad of Celite on a paper
  2. washwashed with MeOH
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in 5 mL of isopropanol
  5. stirringThe reaction mixture was stirred at 70° C. for 3 hours, at which
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was diluted with 120 mL of EtOAc
  8. washwashed with brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude residue was purified by flash chromatography (5% methanol in EtOAc:hexanes=1:1)

출처 및 근거

ORD 기록
ord-2b6f573a55f3405cb1f5d3e420c6340c
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08168794B2

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