Chloride → methyl 3-{4-[2-(acetylmethylamino)thiazol-5-yl]phenyl}-2(S)-ethoxypropanoate

HRID 910294

反応式

HRID 910294 の反応式
[Cl-].Br[C:3]1[S:7][C:6]([N:8](C)[C:9](=O)C)=[N:5][CH:4]=1.[CH2:13]([O:15][C@@H:16]([CH2:21][C:22]1[CH:27]=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][CH:23]=1)[C:17]([O:19][CH3:20])=[O:18])[CH3:14].[F-].[Cs+].CO[CH2:41][CH2:42][O:43]C>>[C:42]([CH2:9][NH:8][C:6]1[S:7][C:3]([C:25]2[CH:24]=[CH:23][C:22]([CH2:21][C@H:16]([O:15][CH2:13][CH3:14])[C:17]([O:19][CH3:20])=[O:18])=[CH:27][CH:26]=2)=[CH:4][N:5]=1)(=[O:43])[CH3:41]

参加物

6

反応物 5

HCID 312ChlorideHCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 67147803N-(5-Bromothiazol-2-yl)-N-methylacetamideHCID 67147872methyl 2(S)-ethoxy-3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]propanoate

生成物 1

HCID 86606237methyl 3-{4-[2-(acetylmethylamino)thiazol-5-yl]phenyl}-2(S)-ethoxypropanoate収率 37%

反応条件

温度
80 °C

実験手順

0.2 g (0.3 mmol) of diphenylphosphinoferrocenepalladium chloride (PdCl2dppf) is added to a solution of 1 g (4.5 mmol) of N-(5-bromothiazol-2-yl)-N-methylacetamide, 1.8 g (6.8 mmol) of methyl 2(S)-ethoxy-3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]propanoate and 1 g (6.8 mmol) of caesium fluoride in 50 ml of ethylene glycol dimethyl ether, degassed beforehand. The reaction medium is heated at 80° C. for 18 hours. After cooling, water is added and the reaction medium is extracted with ethyl acetate. The ethyl acetate phase is washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with a 70/30 and then 60/40 heptane/ethyl acetate mixture. 0.6 g (37%) of methyl 3-{4-[2-(acetylmethylamino)thiazol-5-yl]phenyl}-2(S)-ethoxypropanoate is obtained in the form of a beige-colored solid with a melting point of 123° C.

後処理

  1. customdegassed beforehand
  2. temperatureAfter cooling
  3. additionwater is added
  4. extractionthe reaction medium is extracted with ethyl acetate
  5. washThe ethyl acetate phase is washed with saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue obtained
  10. customis purified by chromatography on a column of silica
  11. washeluted with a 70/30

出典と根拠

ORDレコード
ord-d32f2c1fac174c0da7ddab998a08f7f4
出典データセット
uspto-grants-2011_09
特許番号
US08022079B2

関連ノート

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