反应详情

A mixture of zinc dust (300 mg) in dimethylacetamide (DMA) (0.3 mL) at 50° C. was treated with a solution of chlorotrimethylsilane/1,2-dibromoethane (7/5 v/v, 0.04 mL) and the reaction was stirred at room temperature for 30 minutes. A solution of methyl 2-(tert-butoxycarbonylamino)-3-iodopropanoate (247 mg, 0.75 mmol) in DMA (1 mL) was slowly added and the reaction was stirred for 40 minutes. This mixture was added to a mixture of 95G (35 mg), PdCl2(dppf)2 (7 mg), and CuI (10 mg) in DMA (0.8 mL). The reaction was heated to 80° C. for 18 hours. Water was added and the solid precipitate was collected by filtration. The solid was treated with 33% HBr/AcOH and then concentrate. The residue was dissolved in THF/MeOH and water and treated with LiOH and stirred at room temperature for two hours. The reaction mixture was neutralized with trifluoroacetic acid and purified by preparative reversed phase HPLC to afford the desired product (1.7 mg). Compound 103 had an analytical HPLC retention time=2.906 min. (Chromolith SpeedROD column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.1% TFA, 4 ml/min, monitoring at 220 nm) and a LC/MS M++1=528+.

1. stirringthe reaction was stirred for 40 minutes
2. temperatureThe reaction was heated to 80° C. for 18 hours
3. filtrationthe solid precipitate was collected by filtration
4. additionThe solid was treated with 33% HBr/AcOH
5. concentrationconcentrate
6. dissolutionThe residue was dissolved in THF/MeOH
7. additionwater and treated with LiOH
8. stirringstirred at room temperature for two hours
9. custompurified by preparative reversed phase HPLC