反应详情

A solution of ethyl chloroformate (5.96 g) in anhydrous 2-methyl THF (50 ml) was added drop-wise to a solution of 2,6-dibromo-3-nitro-pyridin-4-ylamine (15.00 g) and triethylamine (10.1 g) in anhydrous 2-methyl THF (100 ml) at 0° C., keeping the addition rate such that the reaction temperature did not rise above 5° C. The reaction mixture was allowed to warm to room temperature then left to stir under nitrogen for 1 hour. A further portion of ethyl chloroformate (0.54 g) was added and the mixture was left to stir for a further 1 hour. Water (50 ml) was added and the layers separated. The aqueous layer was extracted with EtOAc (50 ml) and the combined organics were dried (MgSO4) and evaporated to a brown solid. This solid was pre-absorbed onto silica (˜19 g) then columned on Isco Companion on a silica column (330 g, Redisep), eluting with EtOAc:heptane. The gradient was kept isocractic at 10:90 for 1 column volume (CV), then increased linearly from 10:90 to 30:70 over 6 CVs. This provided the title compound (12.6 g) as a pale yellow foamy solid.

1. customdid not rise above 5° C
2. waitthen left
3. waitthe mixture was left
4. stirringto stir for a further 1 hour
5. customthe layers separated
6. extractionThe aqueous layer was extracted with EtOAc (50 ml)
7. dry with materialthe combined organics were dried (MgSO4)
8. customevaporated to a brown solid
9. customThis solid was pre-absorbed onto silica (˜19 g)
10. washeluting with EtOAc
11. temperatureincreased linearly from 10:90 to 30:70 over 6 CVs