Sodium hydride → 2-{4-[3-(Benzyloxy)-2-{4-[Difluoro(Phosphono)Methyl]Benzyl}-2-(Methoxycarbonyl)-3-Oxopropyl]Phenyl}-2,2-Difluoroacetic Acid

HRID 566500ノート

反応式

HRID 566500 の反応式
C([O:5][P:6]([C:13]([F:37])([F:36])[C:14]1[CH:35]=[CH:34][C:17]([CH2:18][CH:19]([C:30]([O:32][CH3:33])=[O:31])[C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])=[CH:16][CH:15]=1)([O:8]C(C)(C)C)=[O:7])(C)(C)C.[H-].[Na+].Br[CH2:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]([F:57])([F:56])[C:49]([O:51]C(C)(C)C)=[O:50])=[CH:44][CH:43]=1>CN(C=O)C>[CH2:23]([O:22][C:20](=[O:21])[C:19]([CH2:18][C:17]1[CH:16]=[CH:15][C:14]([C:13]([F:37])([F:36])[P:6]([OH:7])([OH:8])=[O:5])=[CH:35][CH:34]=1)([C:30]([O:32][CH3:33])=[O:31])[CH2:41][C:42]1[CH:43]=[CH:44][C:45]([C:48]([F:56])([F:57])[C:49]([OH:51])=[O:50])=[CH:46][CH:47]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 14888669HCID 14888669、化合物HCID 21265687HCID 21265687、化合物

生成物 1

HCID 212657142-{4-[3-(Benzyloxy)-2-{4-[Difluoro(Phosphono)Methyl]Benzyl}-2-(Methoxycarbonyl)-3-Oxopropyl]Phenyl}-2,2-Difluoroacetic Acid

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To starting 1-benzyl 3-methyl 2-{4-[(di-tert-butoxyphosphoryl) (difluoro)methyl]benzyl}malonate (0.12 g) in DMF(5.0 mL) was added NaH (55 mg). The reaction was stirred at r.t. for 30 min. Then tert-butyl 2-[4-(bromomethyl)phenyl]-2,2-difluoroacetate(0.085 g, prepared according the procedures described by J. W. Tilley et al, J. Med. Chem. 1991, 34. 1125) was added to the mixture. After stirring for 2 h, the mixture was quenched with H2O and extracted with EtOAc (50 mL). The extract was dried over Na2SO4 and evaporated to dryness. The residue was treated with a solution of TFA/H2O (3 mL, 9:1) for 3 h at r.t. and evaporated to dryness. The crude was purified on reverse phase HPLC to give 12 mg of the title compound.

後処理

  1. addition1125) was added to the mixture
  2. stirringAfter stirring for 2 h
  3. customthe mixture was quenched with H2O
  4. extractionextracted with EtOAc (50 mL)
  5. dry with materialThe extract was dried over Na2SO4
  6. customevaporated to dryness
  7. additionThe residue was treated with a solution of TFA/H2O (3 mL, 9:1) for 3 h at r.t.
  8. customevaporated to dryness
  9. customThe crude was purified on reverse phase HPLC

出典と根拠

ORDレコード
ord-91d8e940c34545009177ff817be5aa13
出典データセット
uspto-grants-2001_01
特許番号
US06174874B1

反応ノート

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