Dimethyl Sulfate → 3-[4-chloro-2-fluoro-5-(phenylmethoxy)phenyl]-1-methyl-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione

HRID 1450161Notes

Reaction equation

HRID 1450161 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:6][C:5]([N:16]2[C:21](=[O:22])[CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[NH:18][C:17]2=[O:27])=[C:4]([F:28])[CH:3]=1.[CH3:29]OS(OC)(=O)=O.C(=O)(O)[O-].[Na+]>CC(C)=O.CCOCC>[Cl:1][C:2]1[C:7]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:6][C:5]([N:16]2[C:21](=[O:22])[CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[N:18]([CH3:29])[C:17]2=[O:27])=[C:4]([F:28])[CH:3]=1

Participants

6

Reactant 3

HCID 6497Dimethyl SulfateHCID 516892Sodium BicarbonateHCID 199752623-[4-chloro-2-fluoro-5-(phenylmethoxy)phenyl]-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 199752653-[4-chloro-2-fluoro-5-(phenylmethoxy)phenyl]-1-methyl-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedioneYield 62.2%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of 1.85 g (4.46 mmol) of 3-[4-chloro-2-fluoro-5-(phenylmethoxy)phenyl]-6-(trifluoromethyl)-2,4(1H, 3H)-pyrimidinedione, 492 μL (5.20 mmol) of dimethylsulfate, and 749 mg (8.92 mmol) of sodium bicarbonate in 20 mL of acetone was warmed under reflux for 3 h. Evaporation removed the solvent to give a viscous residue. It was dissolved in 50 mL of ether and washed twice with 30 mL of water, dried (MgSO4) and concentrated in vacuo to give white solid which was flash chromatographed over silica gel, eluting with a 1:4 v:v mixture of ethyl acetate and hexane to give 1.19 g of the title compound as a white solid, m.p.: 145°-147° C.; 1H-NMR (CDCl3, 200 MHz) ppm 7.4 (m, 6H), 6.85 (d, 1H), 6.4 (s, 1H), 5.1 (s, 2H), 3.55 (s, 3H).

Workup

  1. temperaturewas warmed
  2. temperatureunder reflux for 3 h
  3. customEvaporation
  4. customremoved the solvent
  5. customto give a viscous residue
  6. washwashed twice with 30 mL of water
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give white solid which
  10. customchromatographed over silica gel
  11. washeluting with a 1:4 v
  12. additionv mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-6c3d524557624a85a4601f3acb1a2407
Source dataset
uspto-grants-1997_02
Patent number
US05602077

Reaction notes

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