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

HRID 566500노트

반응식

HRID 566500 반응식
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

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 14888669HCID 14888669, 화합물HCID 21265687HCID 21265687, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-91d8e940c34545009177ff817be5aa13
출처 데이터셋
uspto-grants-2001_01
특허 번호
US06174874B1

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