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 1626139Notes

Reaction equation

HRID 1626139 reaction equation
[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

Participants

7

Reactant 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

Product 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)-ethanoneYield 92%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 180AcetoneSolvent

Procedure

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]+.

Workup

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

Sources & evidence

ORD record
ord-b5b6ab3450b748358dd362ef8f4188eb
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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