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

HRID 1752989노트

반응식

HRID 1752989 반응식
[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]

참가 물질

10

반응물 4

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

생성물 1

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

시약·촉매·용매 5

HCID 67553Tetrabutylammonium Iodide촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-d0d7e7c8043e4ae5a81d8aee0e6ccaac
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09163042B2

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