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

HRID 2106054노트

반응식

HRID 2106054 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-d6011a8f8cb14447a3ce31a12db348fa
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07579469B2

반응 노트

불러오는 중…