Dimethylformamide → Di-tert-butyl [4-[[2-(4-fluoro-2-methyl-phenoxy)-5-(trifluoromethyl)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate

HRID 1752991Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1752991
[F:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:8]=2[C:9]([NH:11][C:12]2[CH:17]=[CH:16][NH:15][C:14](=[O:18])[CH:13]=2)=[O:10])=[C:4]([CH3:29])[CH:3]=1.ClC([O:33][CH2:34]Cl)=O.CN(C=O)C.[C:41]([O:45][P:46](O[K])([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([CH3:44])([CH3:43])[CH3:42]>C(Cl)Cl.CCOC(C)=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[P:46]([O:33][CH2:34][N:15]1[CH:16]=[CH:17][C:12]([NH:11][C:9](=[O:10])[C:8]2[CH:19]=[C:20]([C:23]([F:26])([F:24])[F:25])[CH:21]=[CH:22][C:7]=2[O:6][C:5]2[CH:27]=[CH:28][C:2]([F:1])=[CH:3][C:4]=2[CH3:29])=[CH:13][C:14]1=[O:18])([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])([O:48][C:49]([CH3:50])([CH3:51])[CH3:52])=[O:47]

Komponenten

9

Edukt 4

HCID 6228DimethylformamideHCID 62754Chloromethyl chloroformate2×HCID 783209072-(4-fluoro-2-methyl-phenoxy)-N-(2-oxo-1H-pyridin-4-yl)-5-(trifluoromethyl)benzamideHCID 178454814HCID 178454814, Verbindung

Produkt 1

HCID 118151653Di-tert-butyl [4-[[2-(4-fluoro-2-methyl-phenoxy)-5-(trifluoromethyl)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphateAusbeute 14,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 2-(4-fluoro-2-methyl-phenoxy)-N-(2-oxo-1H-pyridin-4-yl)-5-(trifluoromethyl)benzamide (10a) (102 mg, 0.2510 mmol) and chloromethyl chloroformate (77.67 mg, 52.30 μL, 0.6024 mmol) in CH2Cl2 (2 mL) was added DMF (200 μL) and the reaction mixture was stirred at room temperature for 1 hour. At this time, more chloromethyl chloroformate (77.67 mg, 52.30 μL, 0.6024 mmol) was added and the reaction mixture was heated to 70° C. for 25 min. The reaction mixture was diluted with EtOAc, the organic phase washed with sat. aq. NaHCO3, brine, dried with Na2SO4 and evaporated to dryness. The residue was taken up in DMF (3 mL), di-tert-butoxyphosphoryloxypotassium (249.3 mg, 1.004 mmol) and tetrabutylammonium iodide (9.271 mg, 0.02510 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 layers 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-[[2-(4-fluoro-2-methyl-phenoxy)-5-(trifluoromethyl)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate (24) (23 mg, 0.03659 mmol, 14.6%) as a clear glass. ESI-MS m/z calc. 628.19617, found 629.5 (M+1)+; Retention time: 0.78 minutes

Aufarbeitung

  1. temperaturethe reaction mixture was heated to 70° C. for 25 min
  2. washthe organic phase washed with sat. aq. NaHCO3, brine
  3. dry with materialdried with Na2SO4
  4. customevaporated to dryness
  5. stirringthe reaction mixture was stirred at 70° C. for 4 hours
  6. temperatureThe reaction mixture was cooled
  7. extractionextracted with EtOAc (3×)
  8. washwashed with water
  9. dry with materialbrine, dried with Na2SO4
  10. customevaporated to dryness
  11. customPurification by column chromatography (12 g silica; 0-100% EtOAc in Hx)

Quellen und Nachweise

ORD-Eintrag
ord-70b9f9fde33a45a4b9d767781fdd01db
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09163042B2

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