Thionyl Chloride → n-butyl 2-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoate

HRID 1193920Notes

Reaction equation

HRID 1193920 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]([C:19]([F:22])([F:21])[F:20])[N:14]=[C:13]2[O:23][CH3:24])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(Cl)(Cl)=O>C1C=CC=CC=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]([C:19]([F:21])([F:20])[F:22])[N:14]=[C:13]2[O:23][CH3:24])=[CH:7][C:3]=1[C:4]([O:6][CH2:10][CH2:2][CH2:3][CH3:4])=[O:5]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 197808272-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoic acid

Product 1

HCID 21270794n-butyl 2-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A suspension of 1.90 g of 2-chloro-4-fluoro-5-[2-methoxy-6 -oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoic acid in 10 ml of benzene and 1.85 g of thionyl chloride is heated for 4 hours while stirring until a solution forms. The reaction mixture is evaporated to dryness under reduced pressure, the residue is dissolved in 20 ml of methylene chloride and the solution is treated at room temperature with 5 ml of n-butanol and 0.50 g of pyridine while stirring. The reaction mixture is stirred for 3 hours and evaporated to dryness under reduced pressure. The residue is dissolved in 100 ml of ethyl acetate, the solution is washed three times with 50 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 silica gel using diethyl ether/n-hexane (1:3) as the eluent. There is obtained n-butyl 2-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoate. 1H-NMR (CDCl3 : 400 MHz): 7.84 ppm (d,1H), 7.40 ppm (d,1H), 6.63 ppm (s,1H), 4.34 ppm (m,2H), 4.02 ppm (s,3H), 1.75 ppm (m,2H), 1.46 ppm (m,2H), 0.97 ppm (t,3H),

Workup

  1. temperatureis heated for 4 hours
  2. customThe reaction mixture is evaporated to dryness under reduced pressure
  3. dissolutionthe residue is dissolved in 20 ml of methylene chloride
  4. additionthe solution is treated at room temperature with 5 ml of n-butanol and 0.50 g of pyridine
  5. stirringwhile stirring
  6. stirringThe reaction mixture is stirred for 3 hours
  7. customevaporated to dryness under reduced pressure
  8. dissolutionThe residue is dissolved in 100 ml of ethyl acetate
  9. washthe solution is washed three times with 50 ml of water each time
  10. dry with materialthe organic phase is dried over anhydrous sodium sulphate
  11. customevaporated to dryness
  12. customThe resinous residue is purified by chromatography on silica gel

Sources & evidence

ORD record
ord-94cd2978eec04365848994af5a0ad0f5
Source dataset
uspto-grants-1989_03
Patent number
US04812164

Reaction notes

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