반응 #11737

반응 방정식

2-chlorosulfonyl-propionic acid ethyl ester

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

triethylamine

dimethylaminopyridine

→

desired product

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

용매

ethyl acetate

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   세척washed with pH 7 phosphate buffer (0.5 M)
2. 2
   건조The organic layer was dried over magnesium sulfate
3. 3
   여과filtered
4. 4
   농축concentrated

실험 절차

To a solution of 2-(2-aminomethyl-4-chloro-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.05 g, 0.119 mmol) in tetrahydrofuran (1 ml) at −40° C. was added triethylamine (0.021 ml, 0.151 mmol), catalytic dimethylaminopyridine and finally a solution of 2-chlorosulfonyl-propionic acid ethyl ester (for preparation, see: Helv. Chim. Acta., (1997) 80, 671 and Bull. Soc. Chim. Fr. (1975), 807) (0.029 g, 0.145 mmol) in tetrahydrofuran (0.25 ml), added over 5 minutes. The reaction was allowed to warm to ambient temperature. After 23 hours the reaction was diluted with ethyl acetate and washed with pH 7 phosphate buffer (0.5 M). The organic layer was dried over magnesium sulfate, filtered and concentrated. The desired product was isolated via silica gel chromatography (0.047 g). This ester (0.07 mmol) was dissolved in 1:1 tetrahydrofuran:water (1 ml) and lithium hydroxide hydrate (5.8 mg, 0.138 mmol) was added. After 21 hours the reaction was concentrated and the title compound obtained after silica gel chromatography (0.039 g, LRMS: 556.1).

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