反应详情

温度

50 °C

A mixture of Zn dust (42 mg) in dimethylacetamide (0.5 mL) was treated with a mixture of chlorotrimethylsilane/1,2-dibromoethane (7/5 v/v, 0.020 mL). The reaction was heated to 50° C. for 30 minutes and then slowly cooled to room temperature. A solution of tert-butyl 4-iodopiperidine-1-carboxylate (165 mg, 0.53 mmol) in dimethylacetamide (1 mL) was added. The reaction was stirred at room temperature for one hour. This solution was added to a mixture of 95G (22 mg), PdCl2(dppf)2 (3 mg), CuI (6 mg) in dimethylactamide (1.2 mL). The reaction was heated under a nitrogen atmosphere at 80° C. for 18 hours. The reaction was diluted with water and extracted with EtOAc. The resulting solid was collected by filtration and the layers were separated. The organic layer was combined with the solid material and concentrated to dryness. The resulting residue was dissolved in CH2Cl2 (1 mL) and treated with trifluoroacetic acid (2 mL). The reaction mixture was concentrated and the residue was purified by preparative reversed phase HPLC (YMC S5 ODS 20×100 mm, 10-90% aqueous methanol over 10 minutes containing 0.1% TFA, 20 ml/min, monitoring at 220 nm). The desired fractions were passed through an SCX cartridge and concentrated to afford the desired compound (1.8 mg). Compound 102 had an analytical HPLC retention time=2.900 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=524+.

1. temperatureslowly cooled to room temperature
2. temperatureThe reaction was heated under a nitrogen atmosphere at 80° C. for 18 hours
3. extractionextracted with EtOAc
4. filtrationThe resulting solid was collected by filtration
5. customthe layers were separated
6. concentrationconcentrated to dryness
7. dissolutionThe resulting residue was dissolved in CH2Cl2 (1 mL)
8. additiontreated with trifluoroacetic acid (2 mL)
9. concentrationThe reaction mixture was concentrated
10. customthe residue was purified by preparative reversed phase HPLC (YMC S5 ODS 20×100 mm, 10-90% aqueous methanol over 10 minutes containing 0.1% TFA, 20 ml/min, monitoring at 220 nm)
11. concentrationconcentrated