Cesium carbonate → 1-[4-Fluoro-2-(trifluoromethyl)phenyl]pyrrolidin-3-ol

HRID 2198042Notes

Reaction equation

HRID 2198042 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[OH:13][CH:14]1[CH2:18][CH2:17][NH:16][CH2:15]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:8][C:5]1[CH:6]=[CH:7][C:2]([N:16]2[CH2:17][CH2:18][CH:14]([OH:13])[CH2:15]2)=[C:3]([C:9]([F:12])([F:11])[F:10])[CH:4]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 982104-HydroxypyrrolidineHCID 5209832-Bromo-5-fluorobenzotrifluorideHCID 634876Binap, (A+-)-

Product 1

HCID 670222871-[4-Fluoro-2-(trifluoromethyl)phenyl]pyrrolidin-3-olYield 84%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 1-bromo-4-fluoro-2-(trifluoromethyl)benzene (4.6 g), 3-hydroxypyrrolidine (1.5 g), palladium(II) acetate (193 mg), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.07 g) and cesium carbonate (16.8 g) in toluene (90 mL) was stirred under an argon gas atmosphere at 85° C. for 16 hr. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 90:10-65:35) to give the title compound (3.58 g, yield 84%) as a yellow oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate 90:10-65:35)

Sources & evidence

ORD record
ord-128399d011ef42668d7d01f0d34e2928
Source dataset
uspto-grants-2012_12
Patent number
US08338622B2

Reaction notes

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