Acetic Acid → Ravuconazole

HRID 222807ノート

反応式

HRID 222807 の反応式
[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]

参加物

5

反応物 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

生成物 1

HCID 467825Ravuconazole収率 38.4%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
70 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-30cce2b0ac5e40679b012cd435abe240
出典データセット
uspto-grants-2012_06
特許番号
US08207352B2

反応ノート

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