反应详情

Under an nitrogen atmosphere, 1.36 g (7.2 mmol) of N-methoxycarbonyl-(L)-tert-leucine (Example 2e), 2.59 g (13.5 mmol) of EDC and 1.22 g (9.0 mmol) of HOBT are dissolved in 20 ml of DMF. After 15 min, 3.79 ml (27 mmol) of TEA are added and then a solution of 2.11 g (4.5 mmol) of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane in 41 ml of DMF is added dropwise. After 3 hours the reaction mixture is concentrated by evaporation. The resulting oil is dissolved in ethyl acetate and a small amount of THF and washed with 2×water, sat. NaHCO3 solution, 2×water and brine. The aqueous phases are extracted with ethyl acetate; the combined organic phases are dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2; methylene chloride/THF 5:1) and crystallisation from ethyl acetate/DIPE yield the title compound: HPLC20-100: tRet=16.0; FAB MS (M+H)+=640.

1. concentrationAfter 3 hours the reaction mixture is concentrated by evaporation
2. dissolutionThe resulting oil is dissolved in ethyl acetate
3. washa small amount of THF and washed with 2×water, sat. NaHCO3 solution, 2×water and brine
4. extractionThe aqueous phases are extracted with ethyl acetate
5. dry with materialthe combined organic phases are dried (Na2SO4)
6. concentrationconcentrated by evaporation
7. customColumn chromatography (SiO2; methylene chloride/THF 5:1) and crystallisation from ethyl acetate/DIPE