反応 #11730

反応方程式

lithium hydroxide hydrate

2-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone

potassium carbonate

chlorosulfonyl-acetic acid ethyl ester

dimethylaminopyridine

→

(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenylsulfamoyl)-acetic acid

溶媒

water

ethyl acetate

dimethylformamide

dimethylformamide

反応条件

後処理

1. 1
   洗浄washed with pH 7.0 phosphate buffer (0.05 M)
2. 2
   乾燥The organic layer was dried over magnesium sulfate
3. 3
   ろ過filtered
4. 4
   濃縮concentrated
5. 5
   workup.DISSOLUTIONThe crude ester was then dissolved in 1:1 tetrahydrofuran
6. 6
   濃縮After 19 hours the reaction was concentrated
7. 7
   その他the title compound purified by silica gel chromatography (0.006 g, LRMS: 528.3)

実験手順

To a solution of 2-(2-amino-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.030 g, 0.074 mmol) in dimethylformamide (0.5 ml) was added potassium carbonate (0.030 g, 0.239 mmol), chlorosulfonyl-acetic acid ethyl ester (0.02 g, 0.12 mmol) (for preparation, see: Helv. Chim. Acta., (1997) 80, 671 and Bull. Soc. Chim. Fr. (1975), 807) in dimethylformamide (0.5 ml) and finally catalytic dimethylaminopyridine. After 23 hours the reaction was diluted with ethyl acetate and washed with pH 7.0 phosphate buffer (0.05 M). The organic layer was dried over magnesium sulfate, filtered and concentrated. The crude ester was then dissolved in 1:1 tetrahydrofuran:water (0.5 ml) and lithium hydroxide hydrate (0.004 g, 0.095 mmol) was added. After 19 hours the reaction was concentrated and the title compound purified by silica gel chromatography (0.006 g, LRMS: 528.3).

出典