4-Methylmorpholine → (S)-1,3'-Bipyrrolidin-1'-YL(4-fluorophenyl)methanone

HRID 1176064노트

반응식

HRID 1176064 반응식
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.CN1CCOCC1.[N:18]1([C@H:23]2[CH2:27][CH2:26][NH:25][CH2:24]2)[CH2:22][CH2:21][CH2:20][CH2:19]1>ClC(Cl)C.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:25]2[CH2:26][CH2:27][C@H:23]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:24]2)=[O:8])=[CH:9][CH:10]=1

참가 물질

5

반응물 3

HCID 79724-MethylmorpholineHCID 99734-Fluorobenzoic AcidHCID 7176274(3S)-3-(Pyrrolidin-1-YL)pyrrolidine

생성물 1

HCID 59725829(S)-1,3'-Bipyrrolidin-1'-YL(4-fluorophenyl)methanone수율 57%

시약·촉매·용매 1

HCID 19746008DMF dichloroethane용매2회

실험 절차

A solution of 4-fluorobenzoic acid (1.5 g, 10.71 mmol) in dichloroethane:DMF (4:1) was treated with O-benzotriazol-1-yl-N,N,N′N′-tetramethlyuronium tetrafluoroborate (4.13 gm 12.85 mmol) and N-methylmorpholine (5.41 g, 53.55 mmol) followed by a solution of (3′S)-1,3′-bipyrrolidine (2.52 g, 11.77 mmol) in dichloroethane:DMF (4:1). The reaction mixture was stirred at room temperature for 3 h and quenched with saturated sodium hydrogen carbonate. The phases were separated. The aqueous phase was extracted with ethyl acetate. The organic phase and the extracts were combined, washed sequentially with water and saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash column chromatography to provide (3′S)-1′-(4-fluorobenzoyl)-1,3′-bipyrrolidine (57%) as a white solid.

후처리

  1. customquenched with saturated sodium hydrogen carbonate
  2. customThe phases were separated
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. washwashed sequentially with water and saturated aqueous sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-6d6b8f2e0c0449b797e70ebed41c4fe4
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842715B2

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