Sodium hydride → HCID 21265714, compound

HRID 566500Notes

Reaction equation

HRID 566500 reaction equation
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

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 14888669HCID 14888669, compoundHCID 21265687HCID 21265687, compound

Product 1

HCID 21265714HCID 21265714, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-91d8e940c34545009177ff817be5aa13
Source dataset
uspto-grants-2001_01
Patent number
US06174874B1

Reaction notes

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