Benzene → thietan-3-yl 2-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoate

HRID 2165799Notes

Reaction equation

HRID 2165799 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:25](Cl)(Cl)=O.[CH:29]1[CH:34]=CC=C[CH:30]=1>CN(C)C=O>[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][CH:29]1[CH2:34][S:25][CH2:30]1)=[O:5]

Participants

5

Reactant 3

HCID 241BenzeneHCID 24386Thionyl ChlorideHCID 197808272-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoic acid

Product 1

HCID 23042385thietan-3-yl 2-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

3.4 g of 2-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H) pyrimidinyl]-benzoic acid are heated at reflux temperature for 3 hours in 25 ml of benzene and 3.4 ml of thionyl chloride together with 2 drops of dimethylformamide. The reaction mixture is subsequently evaporated to dryness and dissolved in 20 ml of dioxan. This solution, which consists mainly of the acid chloride of the above-mentioned benzoic acid and the solvent, is added dropwise to a solution of 1.0 g of 3-thietanol and 1.3 g of pyridine in 20 ml of dioxan. The reaction mixture is then stirred at room temperature for 3.5 hours, treated with 400 ml of water and extracted twice with 400 ml of ethyl acetate each time. The combined organic phases are washed twice with 200 ml of 1N hydrochloric acid each time and once with 200 ml of saturated sodium chloride solution, dried over anhydrous magnesium sulphate and evaporated. The residue is purified by chromatography on silica gel with diethyl ether/n-hexane (1:2). In this manner there is obtained thietan-3-yl 2-chloro-4-fluoro-5-[2-methoxy-6-oxo-4-trifluoromethyl-1(6H)-pyrimidinyl]-benzoate as a colourless oil, 1H-NMR(CDCl3, 400 MHz): 3.37-3.44 (m,2H), 3.57-3.66 (m,2H), 4.03 (s,3H), 5.85 (quintet, 1H), 6.63 (s,1H), 7.42 (d,1H), 7.88 (d,1H).

Workup

  1. customThe reaction mixture is subsequently evaporated to dryness
  2. dissolutiondissolved in 20 ml of dioxan
  3. additionthe solvent, is added dropwise to a solution of 1.0 g of 3-thietanol and 1.3 g of pyridine in 20 ml of dioxan
  4. additiontreated with 400 ml of water
  5. extractionextracted twice with 400 ml of ethyl acetate each time
  6. washThe combined organic phases are washed twice with 200 ml of 1N hydrochloric acid each time
  7. dry with materialonce with 200 ml of saturated sodium chloride solution, dried over anhydrous magnesium sulphate
  8. customevaporated
  9. customThe residue is purified by chromatography on silica gel with diethyl ether/n-hexane (1:2)

Sources & evidence

ORD record
ord-da537586729049308342174768f40c26
Source dataset
uspto-grants-1990_07
Patent number
US04941909

Reaction notes

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