p-Toluenesulfonic acid → Methyl alpha-[6-methyl-4-(3-phenylphenoxy)-5-pyrimidinyl]-beta-methoxyacrylate

HRID 1682539Notes

Reaction equation

HRID 1682539 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:10]=2)[C:3]=1[C:21](=[CH:26]N(C)C)[C:22]([O:24][CH3:25])=[O:23].C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:41](=O)(O)[O-:42].[K+].C(=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>C(OCC)C.O.CN(C)C=O>[CH3:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:10]=2)[C:3]=1[C:21](=[CH:26][O:42][CH3:41])[C:22]([O:24][CH3:25])=[O:23]

Participants

9

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 516893Potassium BicarbonateHCID 53660927Methyl alpha-[4-methyl-6-(3-phenylphenoxy)-5-pyrimidinyl]-beta-dimethylaminoacrylate

Product 1

HCID 54403586Methyl alpha-[6-methyl-4-(3-phenylphenoxy)-5-pyrimidinyl]-beta-methoxyacrylateYield 85%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent

Procedure

Methyl α-[6-methyl-4-(3-phenylphenoxy)-5-pyrimidinyl]-β-dimethylaminoacrylate (60 g, 0.15 mol) is dissolved in diethylether (300 ml) and a solution of p-toluene sulfonic acid (44 g, 0.23 mol) in water (200 ml) is added at room temperature with stirring. After 16 hours the mixture is partially neutralized by adding solid potassium bicarbonate (28 g). Extraction of the product with diethylether, drying of the organic phase (MgSO4) and evaporation of the solvent gives the crude enol (52 g, 93%). The product is dissolved in dimethylformamide (100 ml) and potassium carbonate (33 g, 0.24 mol) and dimethyl sulfate (18.9 g, 0.15 mol) is added with cooling. After stirring the reaction mixture at room temperature for 3 hours, diethylether is added and the mixture is washed repeatedly with bring. Drying and chromatography on silicagel (eluant:hexane/ethyl acetate 1:1) gives the pure methyl α-[6-methyl-4(3-phenylphenoxy)-5-pyrimidinyl]-β-methoxyacrylate as a yellowish oil (46 g, 85%). 1H-NMR (CDCl3):8.60 (s, 1H); 7.66 (s, 1H); 7.60-7.02 (m, 9H); 3.92 (s, 3H); 2.42 (s, 3H).

Workup

  1. extractionExtraction of the product with diethylether
  2. dry with materialdrying of the organic phase (MgSO4) and evaporation of the solvent
  3. customgives the crude enol (52 g, 93%)
  4. temperaturewith cooling
  5. stirringAfter stirring the reaction mixture at room temperature for 3 hours
  6. washthe mixture is washed repeatedly
  7. customDrying

Sources & evidence

ORD record
ord-23c0dd808f55456e975bfac4096e1057
Source dataset
uspto-grants-1997_06
Patent number
US05635508

Reaction notes

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