Dimethyl Sulfoxide → [1,1-Difluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxopentyl]phosphonic acid diethyl ester

HRID 2106054Notes

Reaction equation

HRID 2106054 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:13][P:14]([C:19]([F:36])([F:35])[CH:20]([OH:34])[CH2:21][C:22]([C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[O:32][CH3:33])([CH3:24])[CH3:23])(=[O:18])[O:15][CH2:16][CH3:17])[CH3:12].C(N(CC)CC)C>ClCCl>[CH2:16]([O:15][P:14]([C:19]([F:35])([F:36])[C:20](=[O:34])[CH2:21][C:22]([C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1[O:32][CH3:33])([CH3:23])[CH3:24])(=[O:18])[O:13][CH2:11][CH3:12])[CH3:17]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 57809776[1,1-Difluoro-4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methylpentyl]phosphonic acid diethyl ester

Product 1

HCID 57809801[1,1-Difluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxopentyl]phosphonic acid diethyl esterYield 91.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of oxalyl chloride (2.2 mL, 2.0M in dichloromethane) was diluted with dichloromethane (3.0 mL) and cooled in a dry ice/acetone bath. To this solution was added a solution of DMSO (0.7 mL) in dichloromethane (2.5 mL) dropwise. After 10 minutes, a solution of the [1,1-difluoro-4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methylpentyl]phosphonic acid diethyl ester (1.10 g) in dichloromethane (3 mL) was added and the mixture was stirred for 15 minutes. Triethylamine (4.0 mL) was added, the cooling bath was removed, the reaction mixture was allowed to warm to room temperature and quenched with water and diluted with hexanes. The organic layer was separated, washed with water, dried, filtered, and concentrated in vacuo. The residue was purified by chromatography over silica gel (eluent: hexanes to hexanes-ethyl acetate (2:1) gradient) to give [1,1-difluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxopentyl]phosphonic acid diethyl ester as an oil (1.0 g, 91%).

Workup

  1. temperaturecooled in a dry ice/acetone bath
  2. customthe cooling bath was removed
  3. customquenched with water
  4. additiondiluted with hexanes
  5. customThe organic layer was separated
  6. washwashed with water
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by chromatography over silica gel (eluent: hexanes to hexanes-ethyl acetate (2:1) gradient)

Sources & evidence

ORD record
ord-d6011a8f8cb14447a3ce31a12db348fa
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

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