反应详情

To a solution of 492 mg (1.51 mmol) of N-[bis-(methyl-thio)methylene]-3-t-butylphenylalanine in 5 ml of DMF, 0.183 ml (1.66 mmol) of NMM and 0.159 ml (1.66 mmol) of ethyl chloroformate were added at −15° C. and the mixture was stirred for 30 minutes. The reaction mixture was stirred with bubbling of ammonia gas for another 30 minutes, left to stand at room temperature, diluted with ethyl acetate and washed first with water, then with saturated brine. The organic layer was dried with anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure; the resulting residue was dissolved in 3 ml of 1,4-dioxane and, after adding 1 ml of 2 N hydrochloric acid, the solution was stirred at room temperature for 3 days. Under cooling with ice, the solution was neutralized with saturated aqueous NaHCO3, extracted with chloroform, and washed first with water, then with saturated brine. The organic layer was dried with magnesium sulfate and concentrated under reduced pressure; the resulting residue was subjected to silica gel column chromatography (eluting solvent; chloroform:methanol=10:1) to give Phe(3-tBu)-NH2 in the amount of 210 mg (63%).

1. stirringThe reaction mixture was stirred
2. customwith bubbling of ammonia gas for another 30 minutes
3. waitleft
4. customto stand at room temperature
5. additiondiluted with ethyl acetate
6. washwashed first with water
7. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. dissolutionthe resulting residue was dissolved in 3 ml of 1,4-dioxane
10. additionafter adding 1 ml of 2 N hydrochloric acid
11. stirringthe solution was stirred at room temperature for 3 days
12. temperatureUnder cooling with ice
13. extractionextracted with chloroform
14. washwashed first with water
15. dry with materialThe organic layer was dried with magnesium sulfate
16. concentrationconcentrated under reduced pressure
17. washthe resulting residue was subjected to silica gel column chromatography (eluting solvent; chloroform:methanol=10:1)