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

HRID 724257ノート

反応式

HRID 724257 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-fluoronicotinate

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 (J. Med. Chem., 1993, 36(18), 2676–88) (29 g, 0.143 mol) and 3-methylsulphanyl-phenol (WO 98/45268, pg. 68, preparation 61) (20 g, 0.143 mol) 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.

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-438200328f744bb98da3039fbbb214c1
出典データセット
uspto-grants-2006_11
特許番号
US07141586B2

反応ノート

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