反应详情

温度

-78 °C

To a solution of (E)-5,7-dichloro-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.45 g, 1.28 mmol) in anhydrous THF (20 mL), was added at −78° C. under a N2 atmosphere, a solution of potassium tert-butoxide (1 M in THF, 1.54 mL, 1.54 mmol). After completion of the addition the reaction mixture was stirred for ½ h at −78° C. and a solution of 2-bromobenzylbromide (0.386 mL, 1.54 mmol) in THF (5 mL) was added at −78° C. drop-wise over 15 minutes. The reaction mixture was stirred at −78° C. for 2 more hours and then the temperature was raised to room temperature. The reaction mixture was left at room temperature overnight under a N2 atmosphere. The reaction mixture was quenched with saturated NH4Cl (50 mL) and extracted with EtOAc (3×50 mL). The combined extracts were washed with brine (100 mL), dried (MgSO4) and evaporated in vacuo. The crude material was purified by flash column chromatography (eluted with 20% EtOAc in Hexane) to give (E)-3-(2-bromobenzyl)-5,7-dichloro-1-(4-methoxybenzyl)-1H-benzo[b]azepin-2(3H)-one (0.49 g, 74%) as a pale solid. 1H NMR (400 MHz, DMSO-d6) δ 3.65 (s, 3H), 4.06-4.10 (m, 2H), 4.86 (d, 1H), 5.39 (d, 1H), 4.79 (d, 2H), 6.92 (d, 2H), 7.12-7.39 (m, 3H), 7.54-7.56 (m, 1H), 7.67-7.82 (m, 3H). MS m/z 519.20 [M+1]. Part II:

1. additionAfter completion of the addition the reaction mixture
2. stirringThe reaction mixture was stirred at −78° C. for 2 more hours
3. temperaturethe temperature was raised to room temperature
4. waitThe reaction mixture was left at room temperature overnight under a N2 atmosphere
5. customThe reaction mixture was quenched with saturated NH4Cl (50 mL)
6. extractionextracted with EtOAc (3×50 mL)
7. washThe combined extracts were washed with brine (100 mL)
8. dry with materialdried (MgSO4)
9. customevaporated in vacuo
10. customThe crude material was purified by flash column chromatography (eluted with 20% EtOAc in Hexane)