Ethanethiol → 4(1H)-Pyridinone, 3-(ethylthio)-1-methyl-5-(3-(trifluoromethyl)phenyl)-

HRID 1704636Notes

Reaction equation

HRID 1704636 reaction equation
[O:1]1CCC[CH2:2]1.[CH2:6]([SH:8])[CH3:7].C([Li])CCC.BrCC([C:18]([N:30]([CH2:33][CH3:34])[CH2:31]C)=[CH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=1)=O>C(Cl)(Cl)Cl>[CH2:6]([S:8][C:34]1[C:2](=[O:1])[C:19]([C:20]2[CH:21]=[C:22]([C:26]([F:27])([F:28])[F:29])[CH:23]=[CH:24][CH:25]=2)=[CH:18][N:30]([CH3:31])[CH:33]=1)[CH3:7]

Participants

6

Reactant 4

HCID 6343EthanethiolHCID 8028Tetrahydrofuran3×HCID 86736176HCID 86736176, compoundHCID 178418339Butyllithium

Product 1

HCID 1552694(1H)-Pyridinone, 3-(ethylthio)-1-methyl-5-(3-(trifluoromethyl)phenyl)-

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To 10 ml. of anhydrous tetrahydrofuran at -20° C. were added 1.3 g. of ethanethiol and 13 ml. of 1.6 M n-butyllithium solution and the mixture was stirred under nitrogen for 15 minutes. The solution was allowed to warm to room temperature and a solution of 7.24 g. of α-bromoacetyl-β-diethylamino-3-trifluoromethylstyrene in 10 ml. of tetrahydrofuran was added. The mixture was stirred and heated under reflux overnight. The tetrahydrofuran was stripped off to leave an oil which was dissolved in chloroform and the solution was washed with 1 N hydrochloric acid, 0.1 N sodium hydroxide and saturated sodium chloride. Removal of the chloroform left an oil. One gram of this oil was removed and the remainder was heated under reflux with 25 ml. of N,N-dimethylformamide dimethylacetal for 3 days. The excess dimethylformamide acetal was stripped off and a solution of 5.0 grams of methylamine hydrochloride in 50 ml. of ethanol was added. This solution was heated under reflux for 24 hours. The reaction was poured into methylene chloride and the resulting solution was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and saturated sodium chloride, then dried over magnesium sulfate, filtered, and the solvent stripped. The residue was triturated under diisopropyl ether to give crystalline 3-ethylthio-1-methyl-5 -(α,α,α-trifluoro-m-tolyl)-4(1H)-pyridone, m.p. 84°-85° C. The overall yield was 2.5 g. (40%).

Workup

  1. temperatureheated
  2. temperatureunder reflux overnight
  3. customto leave an oil which
  4. washthe solution was washed with 1 N hydrochloric acid, 0.1 N sodium hydroxide and saturated sodium chloride
  5. customRemoval of the chloroform
  6. waitleft an oil
  7. customOne gram of this oil was removed
  8. temperaturethe remainder was heated
  9. temperatureunder reflux with 25 ml
  10. additionof ethanol was added
  11. temperatureThis solution was heated
  12. temperatureunder reflux for 24 hours
  13. additionThe reaction was poured into methylene chloride
  14. washthe resulting solution was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and saturated sodium chloride
  15. dry with materialdried over magnesium sulfate
  16. filtrationfiltered
  17. customThe residue was triturated under diisopropyl ether

Sources & evidence

ORD record
ord-77f752cedbd94c7f93fd3230545e3c56
Source dataset
uspto-grants-1978_11
Patent number
US04127581

Reaction notes

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