Cesium carbonate → HCID 46941681, compound

HRID 2198028Notes

Reaction equation

HRID 2198028 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.Cl.[OH:17][C@@H:18]1[CH2:22][CH2:21][NH:20][CH2:19]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.O1CCOCC1>[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]([N:20]2[CH2:21][CH2:22][C@@H:18]([OH:17])[CH2:19]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 676021-Bromo-3,5-bis(trifluoromethyl)benzeneHCID 634876Binap, (A+-)-HCID 2759336(3R)-pyrrolidin-3-ol hydrochloride

Product 1

HCID 46941681HCID 46941681, compoundYield 61.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixed solution of 3,5-bis(trifluoromethyl)phenyl bromide (22.0 g), (R)-3-hydroxypyrrolidine hydrochloride (9.23 g), palladium(II) acetate (0.84 g), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4.68 g) and cesium carbonate (73.4 g) in toluene (300 mL)-1,4-dioxane (100 mL) was stirred under an argon gas atmosphere at 80° C. for 16 hr. The solid was filtered off, and the filtrate was washed with saturated brine and water, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate 10:1-3:1) to give the title compound (13.7 g, yield 61%) as a white solid.

Workup

  1. filtrationThe solid was filtered off
  2. washthe filtrate was washed with saturated brine and water
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate 10:1-3:1)

Sources & evidence

ORD record
ord-8e1b22883bff4de7862624238c24287d
Source dataset
uspto-grants-2012_12
Patent number
US08338622B2

Reaction notes

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