Реакция #11730

Уравнение реакции

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

Растворители

water

ethyl acetate

dimethylformamide

dimethylformamide

Условия реакции

Обработка

1. 1
   Промывкаwashed with pH 7.0 phosphate buffer (0.05 M)
2. 2
   СушкаThe organic layer was dried over magnesium sulfate
3. 3
   Фильтрацияfiltered
4. 4
   Концентрированиеconcentrated
5. 5
   workup.DISSOLUTIONThe crude ester was then dissolved in 1:1 tetrahydrofuran
6. 6
   КонцентрированиеAfter 19 hours the reaction was concentrated
7. 7
   Другоеthe title compound purified by silica gel chromatography (0.006 g, LRMS: 528.3)

Методика

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).

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