反应详情

A solution of bis(1,1-dimethylethyl) 2-{3-[(ethyloxy)carbonyl]-6-methyl-2-pyridinyl}-1,4-piperazinedicarboxylate (may be prepared as described in Intermediate 5; 4.96 g) in dichloromethane (200 mL) was cooled to 0° C. and then TFA (20 mL, 260 mmol) was added. This was allowed to warm to room temperature then stirred for 4 hours. The reaction mixture was redissolved in DCM (100 ml), then TFA (10 ml) added and the whole stirred at room temperature for 1.5 hours. The reaction mixture was fully evaporated and azeotroped with toluene. This was dissolved in methanol (200 mL) and then potassium carbonate (3.05 g) was added and the mixture heated to reflux for 8 hours. The methanol was evaporated and then the residue was partitioned between EtOAc and water. The organic layer was then washed with water and then brine, dried through a hydrophobic frit and then evaporated to an orange oil (87 mg), which was found to be impurities.

1. stirringthe whole stirred at room temperature for 1.5 hours
2. customThe reaction mixture was fully evaporated
3. customazeotroped with toluene
4. dissolutionThis was dissolved in methanol (200 mL)
5. additionpotassium carbonate (3.05 g) was added
6. temperaturethe mixture heated
7. temperatureto reflux for 8 hours
8. customThe methanol was evaporated
9. customthe residue was partitioned between EtOAc and water
10. washThe organic layer was then washed with water
11. dry with materialbrine, dried through a hydrophobic frit
12. customevaporated to an orange oil (87 mg), which