Water → 1-[3,5-Bis(trifluoromethyl)phenyl]pyrrolidin-3-ol

HRID 2198020

Reaction equation

HRID 2198020 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5](Br)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH:16][CH:17]1[CH2:21][CH2:20][NH:19][CH2:18]1.CC(C)([O-])C.[Na+].O>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]([N:19]2[CH2:20][CH2:21][CH:17]([OH:16])[CH2:18]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

8

Reactant 4

HCID 962WaterHCID 676021-Bromo-3,5-bis(trifluoromethyl)benzeneHCID 982104-HydroxypyrrolidineHCID 23676156Sodium t-butoxide

Product 1

HCID 752451961-[3,5-Bis(trifluoromethyl)phenyl]pyrrolidin-3-olYield 61.3%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A solution of 3,5-bis(trifluoromethyl)phenyl bromide (21.1 g), 3-hydroxypyrrolidine (6.53 g), tris(dibenzylideneacetone)dipalladium(0) (1.47 g), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.99 g) and sodium tert-butoxide (10.6 g) in toluene (140 ml) was stirred under an argon gas atmosphere at 100° C. for 18 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 95:5-70:30) to give the title compound (13.2 g, yield 61%) as colorless crystals.

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 95:5-70:30)

Sources & evidence

ORD record
ord-6a27d07c863945b19b2ec73161da218e
Source dataset
uspto-grants-2012_12
Patent number
US08338622B2

Linked notes

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