Sodium hydride → Dibenzyl 2,2-di{4-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonate

HRID 566494Notes

Reaction equation

HRID 566494 reaction equation
[C:1]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:13])[CH2:2][C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[H-].[Na+].Br[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([P:35](=[O:46])([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])([F:34])[F:33])=[CH:28][CH:27]=1>CN(C=O)C>[C:42]([O:41][P:35]([C:32]([F:34])([F:33])[C:29]1[CH:30]=[CH:31][C:26]([CH2:25][C:2]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([P:35]([O:36][C:37]([CH3:38])([CH3:40])[CH3:39])([O:41][C:42]([CH3:43])([CH3:44])[CH3:45])=[O:46])([F:34])[F:33])=[CH:28][CH:27]=2)([C:1]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[C:3]([O:5][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[O:4])=[CH:27][CH:28]=1)([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:46])([CH3:43])([CH3:44])[CH3:45]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 84754Dibenzyl malonateHCID 15922636Di(tert-butyl) [4-(bromomethyl)phenyl](difluoro)methylphosphonate

Product 1

HCID 21265761Dibenzyl 2,2-di{4-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonateYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of dibenzyl malonate (0.5 g) in DMF (4 mL), was added sequentially NaH (0.12 g, 80% in mineral oil), di(tert-butyl) [[4-(bromomethyl)phenyl](difluoro)methyl]phosphonate (1.60 g). The reaction mixture was stirred at room temperature for 1 h, then quenched with 20 mL of saturated aqueous NH4Cl solution and extracted with 50 mL EtOAc. The extract was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 1:1 hexane/EtOAc to give the title compound (0.3 g).

Workup

  1. customquenched with 20 mL of saturated aqueous NH4Cl solution
  2. extractionextracted with 50 mL EtOAc
  3. dry with materialThe extract was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography
  6. washeluted with 1:1 hexane/EtOAc

Sources & evidence

ORD record
ord-88d478effc074a75b43cad65e5992102
Source dataset
uspto-grants-2001_01
Patent number
US06174874B1

Reaction notes

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