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 1752979ノート

反応式

HRID 1752979 の反応式
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]

参加物

6

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b968d5e3e19f4fee9e6479426283a9f9
出典データセット
uspto-grants-2015_10
特許番号
US09163042B2

反応ノート

読み込み中…