1H-1,2,4-Triazole → (Alphar,betar)-beta-(2,4-difluorophenyl)-beta-hydroxy-alpha-methyl-1H-1,2,4-triazole-1-butanoic acid

HRID 2260512노트

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HRID 2260512 반응식
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H][H].[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]1([O:23][CH2:22]1)[C@@H:17]([CH3:21])[C:18]([OH:20])=[O:19].[NH4+].[Cl-]>CN(C=O)C.CCCCCC>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@@:16]([OH:23])([CH2:22][N:1]1[CH:5]=[N:4][CH:3]=[N:2]1)[C@@H:17]([CH3:21])[C:18]([OH:20])=[O:19]

참가 물질

7

반응물 4

HCID 92571H-1,2,4-TriazoleHCID 25517Ammonium ChlorideHCID 10353712(2R,3R)-3-(2,4-Difluorophenyl)-3,4-epoxy-2-methylbutanoic acidHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 10040259(Alphar,betar)-beta-(2,4-difluorophenyl)-beta-hydroxy-alpha-methyl-1H-1,2,4-triazole-1-butanoic acid

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8058Hexane용매

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온도
60 °C

실험 절차

To a cooled (0° C.) suspension of Nail (55% mineral oil dispersion, 288 mg, 6.6 mmol, washed with hexane) in DMF (25 mL) was added 1,2,4-triazole (0.5 g, 7.2 mmol) and the mixture was stirred at 0° C. until hydrogen gas ceased to evolve. Then, a solution of unpurified (2R,3R)-3-(2,4-difluorophenyl)-3,4-epoxy-2-methylbutanoic acid (0.5 g) (obtained in reference example 29) in DMF (3 mL) was slowly added and the mixture was heated to 60° C. during 2 h. A saturated NH4Cl aqueous solution was then added and the solvents were removed in vacuo. The mixture was then partitioned between brine containing AcOH and EtOAc. The organic layer was separated and the aqueous phase was extracted with more EtOAc (3x). The collected organic fractions were then dried over anhydrous Na2SO4, the drying agent was filtered and the filtrate was concentrated under reduced pressure to a white solid. Recrystallization from EtOAc afforded the title product as a white solid.

후처리

  1. temperatureTo a cooled
  2. customthe solvents were removed in vacuo
  3. customThe mixture was then partitioned between brine
  4. additioncontaining AcOH and EtOAc
  5. customThe organic layer was separated
  6. extractionthe aqueous phase was extracted with more EtOAc (3x)
  7. dry with materialThe collected organic fractions were then dried over anhydrous Na2SO4
  8. filtrationthe drying agent was filtered
  9. concentrationthe filtrate was concentrated under reduced pressure to a white solid
  10. customRecrystallization from EtOAc

출처 및 근거

ORD 기록
ord-1930ae02423e47d78cb099e8936865c0
출처 데이터셋
uspto-grants-1995_12
특허 번호
US05478826

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