Triethylamine → (3S,5R)-benzyl 3-azido-5-fluoropiperidine-1-carboxylate

HRID 1920178노트

반응식

HRID 1920178 반응식
[F:1][C@@H:2]1[CH2:7][C@@H:6](O)[CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:31]=[N+:32]=[N-:33].[Na+]>ClCCl.C(OCC)C.CCOC(C)=O>[N:31]([C@H:6]1[CH2:7][C@@H:2]([F:1])[CH2:3][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5]1)=[N+:32]=[N-:33]

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 59455657HCID 59455657, 화합물

생성물 1

HCID 59455729(3S,5R)-benzyl 3-azido-5-fluoropiperidine-1-carboxylate수율 90%

시약·촉매·용매 3

HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of (3R,5R)-benzyl 3-fluoro-5-hydroxypiperidine-1-carboxylate (1 eq) in 14 mL of dichloromethane was added triethyl amine (3 eq) and methanesulfonyl chloride (1.5 eq) at 0° C. The reaction mixture was allowed to stir at room temperature for 1.5 hours. The crude mixture was diluted with 120 mL of diethyl ether, washed with sat. aq. sodium bicarbonate, brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was dissolved in 16 mL of NMP. Sodium azide (3.0 eq) was added and the resulting suspension was stirred at 80° C. overnight. The reaction mixture was diluted with 200 mL of EtOAc and 100 mL of hexanes, washed with water, brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (EtOAc:hexanes=1:3) to yield (3S,5R)-benzyl 3-azido-5-fluoropiperidine-1-carboxylate (90%). LC/MS (m/z): 251.1 (MH+-28).

후처리

  1. washwashed with sat. aq. sodium bicarbonate, brine
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude residue was dissolved in 16 mL of NMP
  6. stirringthe resulting suspension was stirred at 80° C. overnight
  7. washwashed with water, brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified by flash chromatography (EtOAc:hexanes=1:3)

출처 및 근거

ORD 기록
ord-803a427635bb4e1facc3dc97f4b56f78
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08168794B2

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