Cesium carbonate → 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone

HRID 1626139Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1626139
[NH2:1][C:2]1[O:3][CH2:4][C:5]([F:21])([F:20])[C@:6]([C:9]2[C:14]([F:15])=[CH:13][C:12]([OH:16])=[C:11]([N+:17]([O-:19])=[O:18])[CH:10]=2)([CH3:8])[N:7]=1.Br[CH2:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][N:27]=1)=[O:25].C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])O.[Na+]>CC(C)=O.[I-].[K+]>[NH2:1][C:2]1[O:3][CH2:4][C:5]([F:20])([F:21])[C@:6]([C:9]2[C:14]([F:15])=[CH:13][C:12]([O:16][CH2:23][C:24]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][N:27]=3)=[O:25])=[C:11]([N+:17]([O-:19])=[O:18])[CH:10]=2)([CH3:8])[N:7]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 111839252-Bromo-1-(5-chloropyridin-2-yl)ethanoneHCID 710088104-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenol

Produkt 1

HCID 710089012-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanoneAusbeute 92 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 4875Potassium IodideKatalysatorHCID 180AcetoneLösungsmittel

Versuchsvorschrift

A dispersion of 4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenol (intermediate F2.1) (120 mg, 393 μmol), 2-bromo-1-(5-chloropyridin-2-yl)ethanone (101 mg, 432 μmol), cesium carbonate (512 mg, 1.57 mmol), and potassium iodide (2 mg, 14.5 μmol) in acetone (5.51 ml) was stirred at room temperature for 20 hours. For the workup, the reaction mixture was poured into a saturated solution of sodium hydrogencarbonate (5 ml) and extracted with dichloromethane (2×5 ml). The combined organic layers were dried over sodium sulphate and evaporated at reduced pressure. The crude 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone (165 mg, 92% yield) was obtained as a red gum. MS (ISP): m/z=459.1 [M+H]+.

Aufarbeitung

  1. extractionextracted with dichloromethane (2×5 ml)
  2. dry with materialThe combined organic layers were dried over sodium sulphate
  3. customevaporated at reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-b5b6ab3450b748358dd362ef8f4188eb
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785436B2

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