4-Methylmorpholine → (S)-1,3'-Bipyrrolidin-1'-YL(4-fluorophenyl)methanone
Reaction equation
[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]=1Participants
Procedure
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.
Workup
- customquenched with saturated sodium hydrogen carbonate
- customThe phases were separated
- extractionThe aqueous phase was extracted with ethyl acetate
- washwashed sequentially with water and saturated aqueous sodium chloride
- dry with materialdried over magnesium sulfate
- concentrationconcentrated in vacuo
- customThe resultant residue was purified by flash column chromatography
Sources & evidence
- ORD record
- ord-6d6b8f2e0c0449b797e70ebed41c4fe4
- Source dataset
- uspto-grants-2010_11
- Patent number
- US07842715B2
Reaction notes
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