Cesium carbonate → 5-Fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid ethyl ester

HRID 1827959ノート

反応式

HRID 1827959 の反応式
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[N:7][C:6]=1Cl)[CH3:2].[CH3:14][S:15][C:16]1[CH:17]=[C:18]([OH:22])[CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[N:7][C:6]=1[O:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([S:15][CH3:14])[CH:17]=1)[CH3:2]

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 99204073-(Methylsulfanyl)phenolHCID 11390082Ethyl 2-chloro-5-fluoronicotinate2 回

生成物 1

HCID 210277065-Fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid ethyl ester

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A solution of ethyl-2-chloro-5-fluoro-nicotinoate (50.4 g, 0.247 mol) (prepared according to the method of J. Med. Chem., 1993, 36(18), 2676–88, page 2684, column 2, 3rd example, ethyl-2-chloro-5-fluoropyridine-3-carboxylate) (29 g, 0.143 mol) and 3-methylsulphanyl-phenol (20 g, 0.143 mol) (prepared according to the method of WO 98/45268, page 68, preparation 61) in dioxane (300 mL) was treated with caesium carbonate (46.5 g, 0.143 mol) at room temperature. The reaction mixture was heated to 100° C. and stirred for 48 hours. The reaction mixture was concentrated in vacuo and the residue taken up in water (600 mL) and extracted with ethyl acetate (3×250 mL). The organics were combined, washed with brine (200 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:toluene (99.75:0.25 to 99.5:0.5) to yield the title product as a yellow oil, 27.1 g (62%).

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. extractionextracted with ethyl acetate (3×250 mL)
  3. washwashed with brine (200 mL)
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:toluene (99.75:0.25 to 99.5:0.5)

出典と根拠

ORDレコード
ord-b5af494f2acb4044a29929634a0e9a18
出典データセット
uspto-grants-2006_06
特許番号
US07056934B2

反応ノート

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