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

HRID 2198054Notes

Reaction equation

HRID 2198054 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([F:12])[CH:3]=1.[OH:13][CH:14]1[CH2:18][CH2:17][NH:16][CH2:15]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[F: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

7

Reactant 3

HCID 10796Cesium carbonateHCID 982104-HydroxypyrrolidineHCID 27363233-Bromo-5-fluorobenzotrifluoride

Product 1

HCID 670223011-[3-Fluoro-5-(trifluoromethyl)phenyl]pyrrolidin-3-olYield 104%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Procedure

A solution of 1-bromo-3-fluoro-5-(trifluoromethyl)benzene (10.0 g), 3-hydroxypyrrolidine (3.58 g), palladium(II) acetate (461 mg), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (2.56 g) and cesium carbonate (26.7 g) in toluene (222 ml) was stirred under an argon gas atmosphere at 90° C. for 16 hr. After cooling to room temperature, the reaction mixture was filtered through celite, and the celite was washed with ethyl acetate. The filtrate and washing were combined and the solution was washed with water and saturated brine. This was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 98:2-20:80) to give the title compound (10.65 g, yield quant.) as a brown oil.

Workup

  1. filtrationthe reaction mixture was filtered through celite
  2. washthe celite was washed with ethyl acetate
  3. washThe filtrate and washing
  4. washthe solution was washed with water and saturated brine
  5. dry with materialThis was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate 98:2-20:80)

Sources & evidence

ORD record
ord-15fa29682b8c4a769b7ba59e7e92e67b
Source dataset
uspto-grants-2012_12
Patent number
US08338622B2

Reaction notes

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