Propargyl bromide → 3-[4-chloro-2-fluoro-5-[(2-propynyl)-oxy]phenyl]-1-methyl-6-(trifluoromethyl)-2,4(1H, 3H)-pyrimidinedione

HRID 1450159Notes

Reaction equation

HRID 1450159 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[C:4]([F:22])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:29](Br)[C:30]#[CH:31]>C(#N)C.C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:7]([O:8][CH2:31][C:30]#[CH:29])=[CH:6][C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:18])([F:17])[F:19])[N:11]([CH3:20])[C:10]2=[O:21])=[C:4]([F:22])[CH:3]=1

Participants

6

Reactant 3

HCID 7842Propargyl bromideHCID 11430Potassium CarbonateHCID 112677571-methyl-6-trifluoromethyl-3-(4-chloro-2-fluoro-5-hydroxyphenyl)-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 199752553-[4-chloro-2-fluoro-5-[(2-propynyl)-oxy]phenyl]-1-methyl-6-(trifluoromethyl)-2,4(1H, 3H)-pyrimidinedione

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 200 mg (0.59 mmol) of 3-[4-chloro-2-fluoro-5-(hydroxy)phenyl]-1-methyl-6- (trifluoromethyl)-2,4 (1H,3H) -pyrimidinedione in 3 mL of acetonitrile was added 162 mg of potassium carbonate (1.18 mmol) and 131 mL (1.18 mmol) of an 80% solution of propargyl bromide in toluene. It was warmed under reflux for 2 h. The resulting mixture was filtered and the filtrate was concentrated in vacuo to give colorless oil which was flash chromatographed over silica gel, eluting with a 1:4 v:v mixture of ethyl acetate and hexane to give 204 mg of title compound as a white foam: 1H-NMR (CDCl3, 200 MHz) ppm 7.35 (d, 1H), 7.0 (d, 1H), 6.4 (s, 1H), 4.78 (d, 2H), 3.58 (s, 3H), 2.6 (d, 1H).

Workup

  1. temperatureIt was warmed
  2. temperatureunder reflux for 2 h
  3. filtrationThe resulting mixture was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customto give colorless oil which
  6. customchromatographed over silica gel
  7. washeluting with a 1:4 v
  8. additionv mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-e4489eb1e791451e988e8fd12bcb3265
Source dataset
uspto-grants-1997_02
Patent number
US05602077

Reaction notes

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