反应详情

温度

-15 °C

N-t-butyloxycarbonyl-L-alanine (3.8 g, 20 m mole), L-proline benzyl ester hydrochloride (5 g, 20.6 m mole) and 1-hydroxy benzotriazole, which is hereinafter referred to as HOBt (2.7 g, 20 m mole) were suspended in tetrahydrofuran, which is hereinafter referred to as THF (50 ml). N,N'-dimethylaminopropylethylcarbodiimide, which is hereinafter referred to as WSC (3.8 ml) in THF (10 ml) solution was added dropwisely to the above suspended solution while cooling with coolant of -15° C. and stirring. The reaction was carried for 3 hours at a temperature of less than 0° C. and thereafter at room temperature overnight. The solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate and washed with 1N hydrochloric acid, water, 5% aqueous sodium bicarbonate and water in order, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was recrystallized in ether-n-hexan to give N-t-butyloxycarbonyl-L-alanyl-L-proline benzyl ester (6.7 g, yield: 89%) having melting point of 71° to 72° C. This product gave one spot by thin layer chromatography (developing solvent; chloroform:methanol:acetic acid=95:5:3, colour forming method; spraying with 0.1% ninhydrin and heating).

1. additionwas added dropwisely to the above suspended solution
2. customat room temperature
3. customovernight
4. customThe solvent was removed by distillation under reduced pressure
5. dissolutionThe residue was dissolved in ethyl acetate
6. washwashed with 1N hydrochloric acid, water, 5% aqueous sodium bicarbonate and water in order
7. dry with materialdried over anhydrous sodium sulfate
8. distillationThe solvent was distilled off under reduced pressure
9. customThe residue was recrystallized in ether-n-hexan