HCID 10710636, compound → HCID 10813782, compound

HRID 1489424Notes

Reaction equation

HRID 1489424 reaction equation
[F:1][C:2]([F:20])([CH:17]([F:19])[F:18])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:15]=[N:14][NH:13][C:12]2=[O:16])=[CH:7][CH:6]=1.[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C:29](=[O:40])[C@@H:30](OS(C(F)(F)F)(=O)=O)[CH3:31]>CN1CCCC1=O.[H-].[Na+].O1CCCC1.C(O)(=O)C.C(OCC)(=O)C>[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C:29](=[O:40])[C@H:30]([N:13]1[C:12](=[O:16])[N:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][CH2:3][C:2]([F:1])([F:20])[CH:17]([F:19])[F:18])=[CH:6][CH:7]=2)[CH:15]=[N:14]1)[CH3:31]

Participants

8

Reactant 2

HCID 10710636HCID 10710636, compoundHCID 10779907HCID 10779907, compound

Product 1

HCID 10813782HCID 10813782, compoundYield 55.5%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 24758Sodium hydrideSolvent

Procedure

4-[4-(2,2,3,3-Tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (6.12 g) was dissolved in 60 ml of 1-methyl-2-pyrrolidone, to which 60% of sodium hydride in oil (0.80 g) was added, and the mixture was stirred at room temperature for 3 hours. The reaction solution was ice-cooled and added dropwise under nitrogen atmosphere over the period of 25 minutes to a solution of 7.32 g of (2S)-2',4'-difluoro-2-trifluoromethanesulfonyloxypropiophenone in 180 ml of tetrahydrofuran which was cooled to -50° C. Then, the reaction temperature was raised to -30° C. over the period of 10 minutes. After stirring for 30 minutes, the reaction solution was diluted with 10 ml of acetic acid and 500 ml of ethyl acetate, washed with water (300 ml×2), 0.5N-hydrochloric acid (400 ml×2) and 300 ml of a saturated aqueous solution of sodium chloride successively, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (silica gel: 250 g, eluent; hexane:ethyl acetate:acetic acid=3:1:0.04), and dissolved in 12 ml of diisopropyl ether. The solution was allowed to stand for 1 hour with ice cooling. The deposited insoluble substance was removed by filtration and the solution was concentrated under reduced pressure to give 5.36 g of 2-[(1R)-2-(2,4-difluorophenyl)-2-oxo-1-methylethyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone as a pale yellow viscous substance.

Workup

  1. additionwas added
  2. temperaturecooled
  3. temperaturewas cooled to -50° C
  4. temperatureThen, the reaction temperature was raised to -30° C. over the period of 10 minutes
  5. stirringAfter stirring for 30 minutes
  6. washwashed with water (300 ml×2), 0.5N-hydrochloric acid (400 ml×2) and 300 ml of a saturated aqueous solution of sodium chloride successively
  7. dry with materialdried over magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customThe residue was purified by silica gel chromatography (silica gel: 250 g, eluent; hexane:ethyl acetate:acetic acid=3:1:0.04)
  10. dissolutiondissolved in 12 ml of diisopropyl ether
  11. waitto stand for 1 hour with ice cooling
  12. customThe deposited insoluble substance was removed by filtration
  13. concentrationthe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2c485e55687a4008b7c95957093cf600
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

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