反应详情

2-(tert Butoxycarbonylmethylamino)-3-(2-naphthyl)propionic acid (1.20 g; 3.55 mmol) was dissolved in methylene chloride (10 ml). 1-Hydroxy-7-azabenzotriazol (0.48 g ;3.55 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.75 g; 3.90 mmol) were added. The reaction mixture was stirred for 15 min at room temperature. 2R)-N-Methyl-2-methylamino-3-(thiophen-2-yl)propionamide (0.70 g; 3.55 mmol) was dissolved in methylene chloride (10 ml) and added. Diisopropylamine (0.61 ml; 3.55 mmol) was added. The reaction mixture was stirred at room temperature for 2 days. Methylene chloride (10 ml) and water (10 ml) were added to the reaction mixture. The phases were separated and the organic phase was washed with aqueous sodium hydrogensulfate (10%; 20 ml), saturated aqueous sodium hydrogencarbonate (20 ml). The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. The crude product was chromatographed on silica (2×20 cm) using ethylacetate/heptane (1:1) as eluent to afford 1.38 g of N-methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-(thiophen-2-yl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl) carbamic acid tert butylester.

1. additionadded
2. stirringThe reaction mixture was stirred at room temperature for 2 days
3. customThe phases were separated
4. washthe organic phase was washed with aqueous sodium hydrogensulfate (10%; 20 ml), saturated aqueous sodium hydrogencarbonate (20 ml)
5. dry with materialThe organic phase was dried over magnesium sulfate
6. customthe solvent was removed in vacuo
7. customThe crude product was chromatographed on silica (2×20 cm)