HCID 10710636, 화합물 → HCID 10813782, 화합물

HRID 1489424노트

반응식

HRID 1489424 반응식
[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]

참가 물질

8

반응물 2

HCID 10710636HCID 10710636, 화합물HCID 10779907HCID 10779907, 화합물

생성물 1

HCID 10813782HCID 10813782, 화합물수율 55.5%

시약·촉매·용매 5

HCID 176Acetic Acid용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매HCID 24758Sodium hydride용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2c485e55687a4008b7c95957093cf600
출처 데이터셋
uspto-grants-1997_10
특허 번호
US05677464

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