Benzene → HCID 23042378, compound

HRID 2165802Notes

Reaction equation

HRID 2165802 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([CH3:19])[N:14]([CH:20]([F:22])[F:21])[C:13]2=[O:23])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(Cl)(Cl)=O.[CH:28]1[CH:33]=CC=C[CH:29]=1>>[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([CH3:19])[N:14]([CH:20]([F:21])[F:22])[C:13]2=[O:23])=[CH:7][C:3]=1[C:4]([O:6][CH2:33][C:28]#[CH:29])=[O:5]

Participants

4

Reactant 3

HCID 241BenzeneHCID 24386Thionyl ChlorideHCID 17990189HCID 17990189, compound

Product 1

HCID 23042378HCID 23042378, compound

Procedure

A suspension of 2.00 g of 2-chloro-5-[3-difluoromethyl-3,6-dihydro-2,6-dioxo-4-methyl -1(2H)-pyrimidinyl]-4-fluorobenzoic acid and 2.05 g of thionyl chloride in 25 ml of benzene is heated at reflux temperature for 20 hours. The clear solution is evaporated to dryness under reduced pressure at 50° C., the residue is dissolved in 20 ml of methylene chloride and subsequently stirred at room temperature for 3.5 hours with 5 ml of propargyl alcohol and 0.55 g of pyridine. The reaction mixture is evaporated to dryness under reduced pressure, the residue is dissolved in 100 ml of ethyl acetate and the solution is extracted three times with 100 ml of water each time. The organic phase is dried over anhydrous sodium sulphate and evaporated to dryness. The resinous residue is purified by chromatography on a silica gel column using diethyl ether/n-hexane (1:1) as the eluent. There is obtained propargyl 2-chloro-5-[3-difluoromethyl-3,6-dihydro-2,6-dioxo-4 -methyl -1(2H)-pyrimidinyl]-4-fluorobenzoate, 1H-NMR (CDCl3, 400 MHz): 7.94 ppm (d, 1H), 7.71 ppm (t, 1H), 7.39 ppm (d, 1H), 5.83 ppm (s, 1H), 4.91 ppm (d, 2H), 2.52 ppm (t, 1H), 2.50 ppm (m, 3H).

Workup

  1. temperatureis heated
  2. temperatureat reflux temperature for 20 hours
  3. customThe clear solution is evaporated to dryness under reduced pressure at 50° C.
  4. dissolutionthe residue is dissolved in 20 ml of methylene chloride
  5. customThe reaction mixture is evaporated to dryness under reduced pressure
  6. dissolutionthe residue is dissolved in 100 ml of ethyl acetate
  7. extractionthe solution is extracted three times with 100 ml of water each time
  8. dry with materialThe organic phase is dried over anhydrous sodium sulphate
  9. customevaporated to dryness
  10. customThe resinous residue is purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-136ef8b83c7f4d66a1a0a52baf067072
Source dataset
uspto-grants-1990_07
Patent number
US04941909

Reaction notes

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