Phenol → 2-Phenoxy-pyrimidine-4-carboxylic acid methyl ester

HRID 2052860Notes

Reaction equation

HRID 2052860 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:10][O:11][C:12]([C:14]1[CH:19]=[CH:18][N:17]=[C:16](S(C)(=O)=O)[N:15]=1)=[O:13]>C1COCC1>[CH3:10][O:11][C:12]([C:14]1[CH:19]=[CH:18][N:17]=[C:16]([O:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:15]=1)=[O:13]

Participants

5

Reactant 3

HCID 996Phenol2×HCID 24758Sodium hydrideHCID 19868790Methyl 2-(methylsulfonyl)pyrimidine-4-carboxylate

Product 1

HCID 205877332-Phenoxy-pyrimidine-4-carboxylic acid methyl esterYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

NaH (3.5 g of a 60% suspension, 87.4 mmol) is added to a solution of phenol (8.23 g, 87.4 mmol) in THF (100 mL) at room temperature. 2-Methanesulfonyl-pyrimidine-4-carboxylic acid methyl ester, 15, (6.3 g, 29.1 mmol) is dissolved in THF (60 mL) and added dropwise to the solution of phenol. The reaction is allowed to stir for 12 hours then quenched by the addition of saturated aqueous NH4Cl. The aqueous phase is extracted with methylene chloride and the combined organic layers are dried, filtered, and concentrated in vacuo to afford a crude oil which is purified over silica (ethyl acetate/hexane 2:3) to afford 1.72 g (25% yield) of the desired product as a white solid.

Workup

  1. customthen quenched by the addition of saturated aqueous NH4Cl
  2. extractionThe aqueous phase is extracted with methylene chloride
  3. customthe combined organic layers are dried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford a crude oil which
  7. customis purified over silica (ethyl acetate/hexane 2:3)

Sources & evidence

ORD record
ord-0fe572dcf8d3434d9b139f0d5f1c1f3f
Source dataset
uspto-grants-2008_02
Patent number
US07326714B2

Reaction notes

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