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

HRID 2106054ノート

反応式

HRID 2106054 の反応式
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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-d6011a8f8cb14447a3ce31a12db348fa
出典データセット
uspto-grants-2009_08
特許番号
US07579469B2

反応ノート

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