反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 95 °C
PROCEDURE
实验过程
To a degassed solution of 3-(3-{3-(3-bromo-benzyl)-2-[tert-butoxycarbonylimino]-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid (0.15 g, 0.25 mmol) in toluene (2 ml) at rt under nitrogen was added Pd(OAc)2 (5 mg, 0.12 mmol) and BINAP (30 mg, 0.048 mmol). Nitrogen was bubbled through the mixture for 10 min before a degassed solution of 1-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazine (90 mg, 0.28 mmol) in toluene (1 ml) was introduced. After 5 min Cs2CO3 (0.84 g, 2.58 mmol) was added. During all additions nitrogen was continuously bubbled through the reaction. Once the additions were completed the reaction vessel was sealed and then heated to 95° C. where it was maintained for 3 h. After this time, the reaction was cooled to rt and additional Pd(OAc)2 (5 mg, 0.12 mmol) and BINAP (30 mg, 0.048 mmol) were introduced. The reaction was then heated to 95° C. where it was maintained for a further 2 h. After this time, the reaction was cooled to rt and filtered through Celite®. The collected solids were washed with dichloromethane and the combined filtrate and washings were concentrated under reduced pressure. The crude product 3-{3-[2-[tert-butoxycarbonylimino]-3-(3-{4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazin-1-yl}-benzyl)-2,3-dihydro-benzoimidazol-1-yl]-propoxy}-benzoic acid (290 mg) was used in the next step without further purification. HPLC-MS 818, 820 [M+1]+.
WORKUP
后处理
- additionwas introduced
- customDuring all additions nitrogen was continuously bubbled through the reaction
- customwas sealed
- temperaturewas maintained for 3 h
- temperatureAfter this time, the reaction was cooled to rt
- temperatureThe reaction was then heated to 95° C. where it
- temperaturewas maintained for a further 2 h
- temperatureAfter this time, the reaction was cooled to rt
- filtrationfiltered through Celite®
- washThe collected solids were washed with dichloromethane
- concentrationthe combined filtrate and washings were concentrated under reduced pressure
- customThe crude product 3-{3-[2-[tert-butoxycarbonylimino]-3-(3-{4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazin-1-yl}-benzyl)-2,3-dihydro-benzoimidazol-1-yl]-propoxy}-benzoic acid (290 mg) was used in the next step without further purification