Application of 145576-28-9, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 145576-28-9 as follows.
To a solution of dry dicyclohexylamine (0.777 mL, 3.90 mmol) in toluene (20 mL) in a round-bottom flask at 0 C. under Ar was added n-butyllithium (2.44 mL, 3.90 mmol) slowly. The reaction was stirred at 0 C. for 30 min. To this prepared lithium dicyclohexylamide solution was added ethyl 4-methylenecyclohexanecarboxylate (555 mg, 3.30 mmol) in toluene (1 mL) slowly over a period of 5 min. The reaction mixture was stirred at 0 C. for additional 30 min to generate the lithium enolate. In a 5 mL pear-shaped flask was placed di-p-bromobis(tri-tert-butylphosphino)dipalladium (I) (1.2 mg, 1.5 mumol) and the flask was capped with a rubber septum. Argon gas was flushed through the flask for 10 min. 1-Bromo-3-phenoxybenzene (747 mg, 3 mmol) in toluene (1 mL) was then added. The resulting solution was transferred via cannula into the round-bottom flask containing the 0 C. THF solution of the lithium enolate of the ethyl ester. Additional toluene (2×0.5 mL) was added to the pear-shaped flask, and this solution was also transferred into the round-bottom flask by cannula. The reaction mixture was allowed to warm to rt and stirred at rt for 3 days. The reaction was quenched with saturated aq. NH4Cl and diluted with EtOAc. The organic layer was washed with water and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by preparative HPLC (PHENOMENEX Axia 5mu C18 30×100 mm column; detection at 220 nm; flow rate=40 mL/min; continuous gradient from 30% B to 100% B over 10 min+2 min hold time at 100% B, where A=90:10:0.1 H2O:MeOH:TFA and B=90:10:0.1 MeOH:H2O:TFA) to afford the title compound (221 mg, 22% yield) as a colorless oil. LCMS, [M+H]+=337.1. 1H NMR (500 MHz, CDCl3) delta 7.38-7.33 (m, 2H), 7.33-7.27 (m, 1H), 7.19-7.10 (m, 3H), 7.04-6.99 (m, 2H), 6.89 (ddd, J=8.0, 2.4, 0.8 Hz, 1H), 4.68 (s, 2H), 4.17 (q, J=7.2 Hz, 2H), 2.61-2.53 (m, 2H), 2.36-2.21 (m, 4H), 1.88-1.79 (m, 2H), 1.22 (t, J=7.0 Hz, 3H).
According to the analysis of related databases, 145576-28-9, the application of this compound in the production field has become more and more popular.
Reference:
Patent; Zhang, Hao; Cheng, Peter T.W.; Chen, Sean; Tao, Shiwei; Wu, Shung C.; Negash, Lidet A.; US2014/275173; (2014); A1;,
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