反应详情

温度

-15 °C

Ac-L-prolyl-L-alanyl-L-proline (1.17 g, 3.61 mmol) was suspended in dry acetonitrile (55 ml) under an argon atmosphere in a flask fitted with an overhead stirrer and internal thermometer. The suspension was cooled to -15° C. and N-methylmorpholine (0.40 ml, 3.61 mmol) was added followed by isobutylchloroformate (0.47 ml, 3.61 mmol) at such a rate as to maintain the internal reaction temperature at -10° to -15° C. Ten minutes after the addition was completed, a mixture of 3-hydroxy-4,4,4-trifluoro-2-butyl-amine hydrochloride (0.65 g, 3.61 mmol) and N-methylmorpho-line (0.40 ml, 3.61 mmol) in chloroform (25 ml) was added at such a rate as to maintain the internal reactiontemperature at -10° to -15° C. The reaction mixture was allowed to warm slowly to room temperature and then stirred at room temperature for 4 hours. The reaction mixture was evaporated on a rotary evaporator to an oily residue which was dissolved in water (65 ml) and treated with a mixed bed resin (J. T. Baker--ANGMI-615, 17 g). After 15 minutes the mixture was filtered and the filtrate evaporated on a rotary evaporator. Chromatography using methylene chloride--10% methanol as the eluent gave the above-named product, (0.37 g) in 23% yield.

1. customfitted with an overhead stirrer
2. temperatureto maintain the internal reaction temperature at -10° to -15° C
3. additionTen minutes after the addition
4. additionwas added at such a rate as
5. temperatureto maintain the internal reactiontemperature at -10° to -15° C
6. temperatureto warm slowly to room temperature
7. customThe reaction mixture was evaporated on a rotary evaporator to an oily residue which
8. dissolutionwas dissolved in water (65 ml)
9. additiontreated with a mixed bed resin (J. T. Baker--ANGMI-615, 17 g)
10. filtrationAfter 15 minutes the mixture was filtered
11. customthe filtrate evaporated on a rotary evaporator
12. customgave the above-named product, (0.37 g) in 23% yield