M-Cresol → (3'S)-1'-[4-(3-methylphenoxy)benzoyl]-1,3'-bipyrrolidine hydrochloride

HRID 1176065Notes

Reaction equation

HRID 1176065 reaction equation
F[C:2]1[CH:19]=[CH:18][C:5]([C:6]([N:8]2[CH2:12][CH2:11][C@H:10]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[CH:20]1[C:25]([OH:26])=[CH:24][CH:23]=[CH:22][C:21]=1[CH3:27].C(=O)([O-])[O-].[K+].[K+].[Cl:34]CCl>CN(C)C=O>[ClH:34].[CH3:27][C:21]1[CH:20]=[C:25]([CH:24]=[CH:23][CH:22]=1)[O:26][C:2]1[CH:19]=[CH:18][C:5]([C:6]([N:8]2[CH2:12][CH2:11][C@H:10]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9]2)=[O:7])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 342M-CresolHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 59725829(S)-1,3'-Bipyrrolidin-1'-YL(4-fluorophenyl)methanone

Product 1

HCID 67141368(3'S)-1'-[4-(3-methylphenoxy)benzoyl]-1,3'-bipyrrolidine hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A solution of (3′S)-1′-(4-fluorobenzoyl)-1,3′-bipyrrolidine (0.011 g, 0.381 mmol in dimethylformamide was treated with m-cresol (0.127 g, 1.14 mmol) and potassium carbonate (0.105 g, 0.762 mmol), heated to 150° C. via microwave radiation for 20 minutes and cooled to room temperature. The reaction mixture was diluted with dichloromethane, 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 (silica, methanol:dichloromethane 5:95) to give the free amine of the title product as a yellow oil. This oil was dissolved in isopropanol and diethyl ether (1:10), treated with 1.0N HCl in diethyl ether and filtered. The filter cake was dried to afford the title product as a yellow solid, 0.021 g (16%), identified by NMR and mass spectral analyses. MS [351.3 m/e (M+H)].

Workup

  1. temperaturecooled to room temperature
  2. washwashed sequentially with water and saturated aqueous sodium chloride
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash column chromatography (silica, methanol:dichloromethane 5:95)

Sources & evidence

ORD record
ord-3c01488734b846c89c0b823403ce476f
Source dataset
uspto-grants-2010_11
Patent number
US07842715B2

Reaction notes

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