Phenol → Ethyl 2-phenoxypyrimidine-5-carboxylate

HRID 1501159Notes

Reaction equation

HRID 1501159 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:19]1([OH:25])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[O:25]([C:2]1[N:7]=[CH:6][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][N:3]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 10796Cesium carbonateHCID 104878152-Chloro-pyrimidine-5-carboxylic acid ethyl ester

Product 1

HCID 89581068Ethyl 2-phenoxypyrimidine-5-carboxylateYield 88.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of ethyl 2-chloropyrimidine-5-carboxylate (0.5 g, 2.7 mmol) in N,N-dimethylformamide (6.0 mL) was added cesium carbonate (676 mg, 2.1 mmol) and phenol (205 mg, 2.18 mmol). The mixture was stirred at 100° C. for 24 hours. The mixture was concentrated in vacuo. To the residue, was added water (50 mL) and extracted with dichloromethane (2*50 mL). The combined organic phase was separated, dried over sodium sulphate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20/1) to give the product ethyl 2-phenoxypyrimidine-5-carboxylate (472 mg, 81%) as colorless oil. 1H NMR (300 MHz, CDCl3): δ 8.55 (s, 2H), 7.43-7.06 (m, 5H), 4.29 (q, J=8.9 Hz, 2H), 1.31 (t, J=8.9 Hz, 3H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionTo the residue, was added water (50 mL)
  3. extractionextracted with dichloromethane (2*50 mL)
  4. customThe combined organic phase was separated
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a residue
  9. customThe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20/1)

Sources & evidence

ORD record
ord-eed4a6da28e34557bd48ab59b6e66cac
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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