Dimethylformamide → Di-tert-butyl [4-[[4-chloro-2-(4-fluoro-2-methyl-phenoxy)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate

HRID 1752989ノート

反応式

HRID 1752989 の反応式
[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=2)=[O:7])=[C:4]([O:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[CH3:26])[CH:3]=1.ClC([O:30][CH2:31]Cl)=O.CN(C=O)C.[C:38]([O:42][P:43](O[K])([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])([CH3:41])([CH3:40])[CH3:39]>C1COCC1.CCOC(C)=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C(Cl)Cl>[P:43]([O:30][CH2:31][N:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6](=[O:7])[C:5]2[CH:16]=[CH:17][C:2]([Cl:1])=[CH:3][C:4]=2[O:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[CH3:26])=[CH:10][C:11]1=[O:15])([O:42][C:38]([CH3:41])([CH3:40])[CH3:39])([O:45][C:46]([CH3:47])([CH3:48])[CH3:49])=[O:44]

参加物

10

反応物 4

HCID 6228DimethylformamideHCID 62754Chloromethyl chloroformateHCID 900347904-chloro-2-(4-fluoro-2-methylphenoxy)-N-(2-oxo-1,2-dihydropyridin-4-yl)benzamideHCID 178454814HCID 178454814、化合物

生成物 1

HCID 118148566Di-tert-butyl [4-[[4-chloro-2-(4-fluoro-2-methyl-phenoxy)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate収率 22.2%

試薬・触媒・溶媒 5

HCID 67553Tetrabutylammonium Iodide触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 4-chloro-2-(4-fluoro-2-methyl-phenoxy)-N-(2-oxo-1H-pyridin-4-yl)benzamide (13a) (99 mg, 0.2656 mmol) and chloromethyl chloroformate (82.19 mg, 55.35 μL, 0.6374 mmol) in THF (2 mL) was added DMF (0.2 mL) and CH2Cl2 (0.5 mL) and was stirred at room temperature for 2 hours. The reaction mixture was diluted with EtOAc and the organic phase washed with sat. aq. NaHCO3, brine, dried with Na2SO4 and evaporated to dryness. The residue was taken up in DMF (1 mL), di-tert-butoxyphosphoryloxypotassium (263.7 mg, 1.062 mmol) and tetrabutylammonium iodide (9.810 mg, 0.02656 mmol) were added and the reaction mixture was stirred at 70° C. for 4 hours. The reaction mixture was cooled, diluted with water and extracted with EtOAc (3×). The organic phases were combined, washed with water then brine, dried with Na2SO4 and evaporated to dryness. Purification by column chromatography (12 g silica; 0-100% EtOAc in Hx) gave di-tert-butyl [4-[[4-chloro-2-(4-fluoro-2-methyl-phenoxy)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate (23) (35 mg, 0.05882 mmol, 22.2%) as a clear foam. ESI-MS m/z calc. 594.1698, found 595.5 (M+1)+; Retention time: 0.77 minutes.

後処理

  1. washthe organic phase washed with sat. aq. NaHCO3, brine
  2. dry with materialdried with Na2SO4
  3. customevaporated to dryness
  4. stirringthe reaction mixture was stirred at 70° C. for 4 hours
  5. temperatureThe reaction mixture was cooled
  6. extractionextracted with EtOAc (3×)
  7. washwashed with water
  8. dry with materialbrine, dried with Na2SO4
  9. customevaporated to dryness
  10. customPurification by column chromatography (12 g silica; 0-100% EtOAc in Hx)

出典と根拠

ORDレコード
ord-d0d7e7c8043e4ae5a81d8aee0e6ccaac
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…