Cesium carbonate → 1-[3-Chloro-5-(trifluoromethyl)phenyl]pyrrolidin-3-ol

HRID 2198053Notes

Reaction equation

HRID 2198053 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[CH:3]=1.[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>[Cl:12][C:4]1[CH:3]=[C:2]([N:16]2[CH2:17][CH2:18][CH:14]([OH:13])[CH2:15]2)[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 982104-HydroxypyrrolidineHCID 634876Binap, (A+-)-HCID 202698551-Bromo-3-chloro-5-(trifluoromethyl)benzene

Product 1

HCID 670222091-[3-Chloro-5-(trifluoromethyl)phenyl]pyrrolidin-3-olYield 80.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 1-bromo-3-chloro-5-(trifluoromethyl)benzene (5.0 g), 3-hydroxypyrrolidine (1.85 g), palladium(II) acetate (217 mg), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.2 g) and cesium carbonate (18.8 g) in toluene (96 mL) was stirred under an argon gas atmosphere at 85° C. for 16 hr. After cooling to room temperature, water was added, 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 80:20-10:90) to give the title compound (4.11 g, yield 80%) as a brown 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 80:20-10:90)

Sources & evidence

ORD record
ord-b36106639f6a4de0b414f5e6b2335ad4
Source dataset
uspto-grants-2012_12
Patent number
US08338622B2

Reaction notes

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