反应详情

To a suspension of 17.2 g 4-(((9H-fluorene-9-yl)methoxy)carbonylamino)-2-nitrobenzoic acid in 222 ml dichloromethane were added 17.7 g of N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)-uronium-hexafluoro-phosphate. After stirring for 15 min. at room temperature a solution of 13.8 g of L-glutamic acid-di-tert.butylester hydrochloride in 172 ml dichloromethane and 12.9 ml triethylamine were added dropwise within 30 min. The mixture was stirred under nitrogen at room temperature for 20 hours. After addition of 860 ml of methyl-tert.-butylether the mixture was washed five times with aqueous sodium H carbonate (5%), 5 times with aqueous citric acid (5%) and two times with brine. The organic layer was dried over magnesium sulphate and evaporated to dryness under vacuum to give 27.9 g of crude di-tert-butyl 2-(4-(((9H-fluorene-9-yl)methoxy)carbonylamino)-2-nitrobenzamido)-L-glutamate as a yellow foam. The crude product was purified by flash chromatography using silica gel 60 and ethylacetate/n-heptane/45:55 as eluent. After evaporation of product fractions 23.8 g of di-tert-butyl-N-(4-(((9H-fluorene-9-yl)methoxy)carbonylamino)-2-nitrobenzamido)-L-glutamate were obtained as a yellow foam (HPLC, purity: 99.9% area).

1. additionwere added dropwise within 30 min
2. washwas washed five times with aqueous sodium H carbonate (5%), 5 times with aqueous citric acid (5%) and two times with brine
3. dry with materialThe organic layer was dried over magnesium sulphate
4. customevaporated to dryness under vacuum