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 1626139ノート

反応式

HRID 1626139 の反応式
[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

参加物

7

反応物 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

生成物 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)-ethanone収率 92%

試薬・触媒・溶媒 2

HCID 4875Potassium Iodide触媒HCID 180Acetone溶媒

実験手順

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]+.

後処理

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

出典と根拠

ORDレコード
ord-b5b6ab3450b748358dd362ef8f4188eb
出典データセット
uspto-grants-2014_07
特許番号
US08785436B2

反応ノート

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