Phosphate → HCID 178462430、化合物

HRID 1766898ノート

反応式

HRID 1766898 の反応式
N1([C:6]([O:8][C@:9]([C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=2[F:45])([CH2:32][N:33]2[CH:37]=[N:36][CH:35]=[N:34]2)[C@H:10]([S:12][C@@H:13]2[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][C:24]=3[F:31])[O:15][CH2:14]2)[CH3:11])=[O:7])C=CN=C1.[Si:46]([O:63][CH2:64][CH2:65][OH:66])([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.P([O-])([O-])([O-])=O>ClCCl.CC(C)([O-])C.[K+]>[C:6](=[O:7])([O:8][C@:9]([C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=1[F:45])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[C@H:10]([S:12][C@@H:13]1[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]2[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][C:24]=2[F:31])[O:15][CH2:14]1)[CH3:11])[O:66][CH2:65][CH2:64][O:63][Si:46]([C:59]([CH3:62])([CH3:61])[CH3:60])([C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

参加物

6

反応物 3

HCID 1061PhosphateHCID 151562692-((tert-Butyldiphenylsilyl)oxy)ethanolHCID 178462428HCID 178462428、化合物

生成物 1

HCID 178462430HCID 178462430、化合物収率 73%

試薬・触媒・溶媒 2

HCID 23665647Potassium tert-butoxide触媒HCID 6344Dichloromethane溶媒

実験手順

(1R,2R)-2-[[trans-2-[(1E,3E)-4-(4-Cyano-2-fluorophenyl)-1,3-butadienyl]-1,3-dioxan-5-yl]thio]-1-(2,4-difluorophenyl)-1-[(1H-1,2,4-triazol-1-yl)methyl]propyl imidazole-1-carboxylate (637 mg, 1.00 mmol) obtained from Example 15-(1) and the crude 2-[(tert-butyldiphenylsilyl)oxy]ethanol (315 mg, ca. 1.05 mmol) obtained from Example 15-(2) were dissolved in dichloromethane (3 ml), and potassium tert-butoxide (5 mg) was added thereto. The mixture was heated under reflux for 15 minutes with stirring. After cooling, a phosphate buffer solution (pH 7) was poured into the mixture, and the reaction product was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform] to afford the title compound (631.4 mg, 73% yield) as a colorless amorphous solid.

後処理

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 15 minutes
  3. temperatureAfter cooling
  4. extractionthe reaction product was extracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform]

出典と根拠

ORDレコード
ord-53349c4320cc47a6bee39377e65ac0ab
出典データセット
uspto-grants-2007_06
特許番号
US07230023B2

反応ノート

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