反应详情

Under a nitrogen atmosphere, 938 mg (4.96 mmol) of N-methoxycarbonyl-(L)-iso-leucine, 1.78 g (9.3 mmol) of EDC and 838 mg (6.2 mmol) of HOBT are dissolved in 13.7 ml of DMF. After 30 min, 2.6 ml (18.6 mmol) of TEA are added and then a solution of 1.45 g (3.1 mmol) of 1-[4-(thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane (Example 17b) in 28 ml of DMF is added dropwise thereto. After 3 hours the reaction mixture is concentrated by evaporation; the residue is taken up in ethyl acetate and a small amount of THF and washed with water, sat. NaHCO3 solution, water and brine. The aqueous phases are extracted with ethyl acetate; the combined organic phases are dried over Na2SO4 and concentrated by evaporation. Column chromatography (SiO2; methylene chloride/THF 5:1) and stirring from ethyl acetate/DIPE yield the title compound: HPLC20-100: tRet=16.3; FAB MS (M+H)+=640.

1. concentrationAfter 3 hours the reaction mixture is concentrated by evaporation
2. washa small amount of THF and washed with water, sat. NaHCO3 solution, water and brine
3. extractionThe aqueous phases are extracted with ethyl acetate
4. dry with materialthe combined organic phases are dried over Na2SO4
5. concentrationconcentrated by evaporation