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

HRID 2220932Notes

Reaction equation

HRID 2220932 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-d2fe3051ed274aa995c70e2298585cdf
Source dataset
uspto-grants-2008_05
Patent number
US07368455B2

Reaction notes

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