Phosphate → HCID 178462428、化合物

HRID 1766896ノート

反応式

HRID 1766896 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([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:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=2[F:31])[O:15][CH2:14]1)[CH3:11].[C:39](N1C=CN=C1)([N:41]1[CH:45]=[CH:44][N:43]=[CH:42]1)=[O:40].P([O-])([O-])([O-])=O>ClCCl.[H-].[Na+]>[N:41]1([C:39]([O:38][C@:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])([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:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=3[F:31])[O:15][CH2:14]2)[CH3:11])=[O:40])[CH:45]=[CH:44][N:43]=[CH:42]1

参加物

6

反応物 3

HCID 1061PhosphateHCID 682631,1'-CarbonyldiimidazoleHCID 178462432HCID 178462432、化合物

生成物 1

HCID 178462428HCID 178462428、化合物収率 70%

試薬・触媒・溶媒 2

HCID 24758Sodium hydride触媒HCID 6344Dichloromethane溶媒

実験手順

4-[(1E,3E)-4-[trans-5-[[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-1,3-butadienyl]-3-fluorobenzonitrile (4.90 g, 9.03 mmol) described in Reference example 1 and 1,1′-carbonyldiimidazole (1.53 g, 9.44 mmol) were dissolved in dichloromethane (20 ml). To the mixture was added sodium hydride (55% dispersion in mineral oil; 10 mg, 2.3×10−4 mol), and the reaction mixture was heated under reflux for 3 hours with stirring. After cooling, a phosphate buffer solution (pH 7.4) was added thereto, and the product was extracted with ethyl acetate. The organic layer was washed with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel (120 g) column (eluent; ethyl acetate:hexane=1:1˜1:0) to afford the title compound (4.00 g, 70% yield) as a colorless amorphous solid.

後処理

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 3 hours
  3. temperatureAfter cooling
  4. extractionthe product was extracted with ethyl acetate
  5. washThe organic layer was washed with an aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure

出典と根拠

ORDレコード
ord-1d00c442ba914392ba35835e03768ae2
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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