Sodium hydride → 1-[(1R,2R)-1-Methyl-2-hydroxy-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-4-imidazoline-2-one

HRID 1077906

반응식

HRID 1077906 반응식
[H-].[Na+].[F:3][C:4]([F:21])([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH:19]=[CH:18][NH:17][C:16]2=[O:20])=[CH:11][CH:10]=1)[CH:5]([F:7])[F:6].[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[C@@:30]1([CH2:34][N:35]2[CH:39]=[N:38][CH:37]=[N:36]2)[C@H:32]([CH3:33])[O:31]1>>[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[C@@:30]([OH:31])([CH2:34][N:35]1[CH:39]=[N:38][CH:37]=[N:36]1)[C@H:32]([N:17]1[CH:18]=[CH:19][N:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][C:4]([F:3])([F:21])[CH:5]([F:6])[F:7])=[CH:10][CH:11]=2)[C:16]1=[O:20])[CH3:33]

참가 물질

4

반응물 3

HCID 24758Sodium hydrideHCID 101311911-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-HCID 105643671-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone

생성물 1

HCID 30036201-[(1R,2R)-1-Methyl-2-hydroxy-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-4-imidazoline-2-one수율 36%

실험 절차

60% Sodium hydride in oil (2.4 g) was added portionwise to a stirred solution of 1-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone (16.6 g) and the resulting mixture was stirred for 30 minutes at room temperature. (2R,3S)-2-(2,4-Difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane (10 g) was added and the mixture was stirred at 80° C. for 20 hours. After cooling, the mixture was concentrated into a volume of about 50 ml under reduced pressure and diluted ice-water (400 ml) and ethyl acetate (500 ml). The ethyl acetate layer was separated, washed with a 10% aqueous phosphoric acid solution (400 ml) and an aqueous solution of sodium chloride (400 ml×2) successively and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/1 to 2/1) to give 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone (7.56 g) as an oily substance, which was identical with the compound obtained in the Reference Example 47.

후처리

  1. stirringthe mixture was stirred at 80° C. for 20 hours
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated into a volume of about 50 ml under reduced pressure and diluted ice-water (400 ml) and ethyl acetate (500 ml)
  4. customThe ethyl acetate layer was separated
  5. washwashed with a 10% aqueous phosphoric acid solution (400 ml)
  6. dry with materialan aqueous solution of sodium chloride (400 ml×2) successively and dried over anhydrous magnesium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/1 to 2/1)

출처 및 근거

ORD 기록
ord-71bae1d6ab22408a841bc96f4a13e146
출처 데이터셋
uspto-grants-1996_08
특허 번호
US05545652

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