Cesium carbonate → 2-(3-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenoxy)ethanol

HRID 2067899Notes

Reaction equation

HRID 2067899 reaction equation
[F:1][CH:2]([F:24])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=3)=[N:14][CH:15]=2)=[CH:6][CH:5]=1.Br[CH2:26][CH2:27][OH:28].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[F:24][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[N:14][C:13]([NH:16][C:17]3[CH:18]=[C:19]([CH:20]=[CH:21][CH:22]=3)[O:23][CH2:26][CH2:27][OH:28])=[N:12][CH:11]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 108982-BromoethanolHCID 687295593-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenol

Product 1

HCID 687282992-(3-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenoxy)ethanol

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenol 39 (1.2 mmol), 2-bromoethanol (1.4 mmol) and cesium carbonate (1.6 mmol) in acetonitrile (10 mL) is heated to 85° C. for 12 h then cooled to rt. The reaction is evaporated to dryness then re-dissolved in DCM. The organic mixture is washed with water and brine then dried over magnesium sulfate, filtered and reduced to dryness. Purification by silica gel chromatography with hexane:EtOAc=1:1 as eluant affords 2-(3-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenoxy)ethanol 40a as white solid. MS (m/z) (M+1)+: 373.8.

Workup

  1. customThe reaction is evaporated to dryness
  2. dissolutionthen re-dissolved in DCM
  3. washThe organic mixture is washed with water and brine
  4. dry with materialthen dried over magnesium sulfate
  5. filtrationfiltered
  6. customPurification by silica gel chromatography with hexane

Sources & evidence

ORD record
ord-77cc3b521a5e4bbdb994ecb109001f92
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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