Sodium hydride → 2,2-Di{4-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonic Acid, Benzyl Methyl Ester

HRID 566493Notes

Reaction equation

HRID 566493 reaction equation
[C:1]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([P:29](=[O:40])([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])([F:28])[F:27])=[CH:22][CH:21]=1>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[I-]>[C:36]([O:35][P:29]([C:26]([F:28])([F:27])[C:23]1[CH:24]=[CH:25][C:20]([CH2:19][C:2]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]([P:29]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:40])([F:28])[F:27])=[CH:22][CH:21]=2)([C:3]([O:5][CH3:6])=[O:4])[C:1]([O:8][CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:7])=[CH:21][CH:22]=1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:40])([CH3:37])([CH3:38])[CH3:39]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 5721351-Benzyl 3-methyl propanedioateHCID 15922636Di(tert-butyl) [4-(bromomethyl)phenyl](difluoro)methylphosphonate

Product 1

HCID 867562362,2-Di{4-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonic Acid, Benzyl Methyl Ester

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of benzyl methyl malonate (0.2 g) in DMF (8 mL), was added sequentially NaH (0.08 g, 60% in mineral oil), di(tert-butyl) [[4-(bromomethyl)phenyl](difluoro)methyl]phosphonate (0.83 g), and n-Bu4NI (0.08 g). The reaction mixture was stirred at room temperature for 2.5 h, then quenched with 20 mL of saturated aqueous NH4Cl solution and extracted with 50 mL of 1:1 hexane/EtOAc. The extract was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 2:1 hexane/EtOAc. First eluted was 1-benzyl 3-methyl 2-{4-[(di-tert-butoxyphosphoryl)(difluoro)methyl]benzyl}malonate (0.2 g), followed by the title compound (0.3 g) as an oil.

Workup

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

Sources & evidence

ORD record
ord-645167a4e56f4bba930a8080981ac22a
Source dataset
uspto-grants-2001_01
Patent number
US06174874B1

Reaction notes

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