Acetic Acid → Ravuconazole

HRID 222807노트

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HRID 222807 반응식
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([CH:14]([CH3:31])[C:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([OH:22])[CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)[S:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].[C@@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(O)(=O)C>CO>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([C@H:14]([CH3:31])[C@:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])([OH:22])[CH2:16][N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)[S:12][CH:13]=2)=[CH:5][CH:4]=1)#[N:2]

참가 물질

5

반응물 3

HCID 176Acetic AcidHCID 131278(R)-camphorsulfonic acidHCID 98459224-[2-[3-(2,4-Difluorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butan-2-yl]-1,3-thiazol-4-yl]benzonitrile

생성물 1

HCID 467825Ravuconazole수율 38.4%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
70 °C

실험 절차

Racemic 3-[4-(4-cyanophenyl)thiazol-2-yl]-1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-butan-2-ol (44 g) and (1R)-10-camphorsulfonic acid (20 g) were suspended in methanol (ca. 300 ml), the slurry was stirred intensively, warmed up to ca. 70° C. and a small addition of acetic acid was added to obtain a clear solution. After cooling of the solution to rt and then to 0° C., the mixture was seeded with enantiomerically pure salt and stirred for another 2 hrs. The crystalline solid was collected by filtration, washed with cooled methanol and dried under reduced pressure. The crystals were partitioned between methylenechloride (300 ml) and saturated aqueous sodium bicarbonate solution (200 ml). The organic layer was washed twice with water (50 ml), dried with magnesium sulphate, filtrated and evaporated under reduced pressure to give the title compound (16.9 g, 38% yield, 95% ee). The analytical data were identical with published (U.S. Pat. No. 5,648,372 or Chem. Pharm. Bull. 1998, 46, 623).

후처리

  1. additionwas added
  2. customto obtain a clear solution
  3. temperatureAfter cooling of the solution to rt
  4. customto 0° C.
  5. stirringstirred for another 2 hrs
  6. filtrationThe crystalline solid was collected by filtration
  7. washwashed with cooled methanol
  8. customdried under reduced pressure
  9. customThe crystals were partitioned between methylenechloride (300 ml) and saturated aqueous sodium bicarbonate solution (200 ml)
  10. washThe organic layer was washed twice with water (50 ml)
  11. dry with materialdried with magnesium sulphate
  12. filtrationfiltrated
  13. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-30cce2b0ac5e40679b012cd435abe240
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08207352B2

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