N-[1-(chloromethyl)-2-oxo-4-pyridyl]-2-(4-fluoro-2-methyl-phenoxy)-4-(trifluoromethyl)benzamide → Di-tert-butyl [4-[[2-(4-fluoro-2-methyl-phenoxy)-4-(trifluoromethyl)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate

HRID 1752979노트

반응식

HRID 1752979 반응식
Cl[CH2:2][N:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:30])[C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=2[O:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[CH3:29])=[CH:5][C:4]1=[O:31].[C:32]([O:36][P:37]([O:44][K])([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])([CH3:35])([CH3:34])[CH3:33]>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[P:37]([O:44][CH2:2][N:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:30])[C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=2[O:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[CH3:29])=[CH:5][C:4]1=[O:31])([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])([O:39][C:40]([CH3:42])([CH3:43])[CH3:41])=[O:38]

참가 물질

6

반응물 2

HCID 118126598N-[1-(chloromethyl)-2-oxo-4-pyridyl]-2-(4-fluoro-2-methyl-phenoxy)-4-(trifluoromethyl)benzamideHCID 178454814HCID 178454814, 화합물

생성물 1

HCID 118126612Di-tert-butyl [4-[[2-(4-fluoro-2-methyl-phenoxy)-4-(trifluoromethyl)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate수율 45%

시약·촉매·용매 3

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
70 °C

실험 절차

The crude N-[1-(chloromethyl)-2-oxo-4-pyridyl]-2-(4-fluoro-2-methyl-phenoxy)-4-(trifluoromethyl)benzamide from the previous step was taken up in N,N-dimethylformamide (5 mL). Di-tert-butoxyphosphoryloxypotassium (496.6 mg, 2.0 mmol) and tetrabutylammonium iodide (36.94 mg, 0.10 mmol) were added and the reaction mixture was stirred at 70° C. for 4 hours. The reaction mixture was then diluted with ethyl acetate and washed with water then brine, dried with Na2SO4, filtered and evaporated to dryness. The material was purified by column chromatography (40 g silica, 50-100% EtOAc in Hexanes), fractions with the product were pooled and evaporated to give di-tert-butyl [4-[[2-(4-fluoro-2-methyl-phenoxy)-4-(trifluoromethyl)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate (20) (280 mg, 45%) as a yellow oil that was used in the next step without further purification. ESI-MS m/z calc. 628.20, found 629 (M+1)+; Retention time: 0.76 minutes (1 minute run).

후처리

  1. washwashed with water
  2. dry with materialbrine, dried with Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe material was purified by column chromatography (40 g silica, 50-100% EtOAc in Hexanes), fractions with the product
  6. customevaporated

출처 및 근거

ORD 기록
ord-b968d5e3e19f4fee9e6479426283a9f9
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09163042B2

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