Cesium carbonate → 5-Bromo-3-(pyrimidin-2-ylmethoxy)benzo[d]isoxazole

HRID 1482864Notes

Reaction equation

HRID 1482864 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][N:8]=[C:7]([OH:10])[C:6]=2[CH:11]=1.Cl.Cl[CH2:14][C:15]1[N:20]=[CH:19][CH:18]=[CH:17][N:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][N:8]=[C:7]([O:10][CH2:14][C:15]3[N:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:6]=2[CH:11]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 200256062-(Chloromethyl)pyrimidine hydrochlorideHCID 178518981HCID 178518981, compound

Product 1

HCID 1181619695-Bromo-3-(pyrimidin-2-ylmethoxy)benzo[d]isoxazoleYield 41.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-bromobenzo[d]isoxazol-3-ol (200 mg, 0.93 mmol), 2-(chloromethyl)pyrimidine hydrochloride (200 mg, 1.21 mmol) and cesium carbonate (1 g) were combined in 10 mL DMF and stirred at ambient temperature for two days. The reaction mixture was diluted with 60 mL ethyl acetate, washed with water and brine and evaporated under vacuum. Flash chromatographic purification on 12 g silica gel with 0-100% ethyl acetate in hexane gave O-alkylated product 5-bromo-3-(pyrimidin-2-ylmethoxy)benzo[d]isoxazole (120 mg, 0.39 mmol).

Workup

  1. washwashed with water and brine
  2. customevaporated under vacuum
  3. customFlash chromatographic purification on 12 g silica gel with 0-100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-821dc7f0a30e48dc8e9cbf8cbcbc6b56
Source dataset
uspto-grants-2016_08
Patent number
US09416115B2

Reaction notes

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