反应详情

To a solution of 2-((tert-butoxycarbonyl)amino)-3-hydroxy-2-methylpropanoic acid (Preparation 53, 186 mg, 0.85 mmol) acetonitrile (4.0 mL) and 4-methylmorpholine (0.15 mL, 1.4 mmol) cooled in an ice/brine bath was added isobutylchloroformate (0.050 mL, 0.38 mmol). The mixture was stirred for 30 minutes and then 4-neopentylbenzene-1,2-diamine (Preparation 83, 139 mg, 0.78 mmol) was added. The reaction mixture was allowed to warm to room temperature and stir for 4 days. The solvent was evaporated and the resulting oil was dissolved in acetic acid (3.0 mL, 50 mmol) and stirred at room temperature for 16 hours and then heated to 70° C. for 5 hours. After cooling, the solvent was removed in vacuo and the residue purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient. The resulting oil was dissolved in methylene chloride (5 mL) and treated with trifluoroacetic acid (0.5 mL, 6 mmol). After stirring for 2 hours, the reaction mixture was concentrated in vacuo and purified by silica gel column chromatography eluting with a 0-100% CMA80/methylene chloride gradient to provide the title compound (20.6 mg, 10%) as an off-white solid.

1. stirringstir for 4 days
2. customThe solvent was evaporated
3. stirringstirred at room temperature for 16 hours
4. temperatureheated to 70° C. for 5 hours
5. temperatureAfter cooling
6. customthe solvent was removed in vacuo
7. customthe residue purified by silica gel column chromatography
8. washeluting with a 0-100% ethyl acetate/hexanes gradient
9. dissolutionThe resulting oil was dissolved in methylene chloride (5 mL)
10. stirringAfter stirring for 2 hours
11. concentrationthe reaction mixture was concentrated in vacuo
12. custompurified by silica gel column chromatography
13. washeluting with a 0-100% CMA80/methylene chloride gradient