Synthetic Route of 1254319-51-1,Some common heterocyclic compound, 1254319-51-1, name is 6-Bromo-2-methylisoindolin-1-one, molecular formula is C9H8BrNO, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a solution of 6-bromo-2-methylisoindolin-1-one (5 g,22.1 mmol) in dmf (30 mL) was added bis(pinacolato)diboron (6.18 g,24.3 mmol) and potassium acetate (6.51 g,66.4 mmol). The reaction mixture was degassed and backfilled with N2 gas,and 1,1 ?-bis(diphenylphosphino)fenocene palladium(II)dichloride dichloromethane (0.903 g,1.106 mmol) was added.The reaction mixture was stined at 80 C for 10 hours. After diluting with EtOAc and water, The organic layer was concentrated and purified on silica column (100% EtOAc) to get the product as a mixture of the title compound as a boronic ester and boronic acid,which was not further purified.MS: 274 (m+1)?H NMR (500 MHz,CDCl3): oe 8.33 (s,1H),7.98 (d,7.5 Hz,1H),7.46 (d,7.5 Hz,1H),4.41 (s,2H),3.22 (s,3H),1.38 (s,12H). The following intermediates in table c were preparedaccording to scheme c using the procedure outlined in the synthesis intermediate cl using 1,1?-bis(di-tert-butylphosphino)fenocene palladium dichloride or 1,1 ?-bis(diphenylphosphino)ferrocene palladium(II)dichloride dichloromethane complex as the palladium catalyst with toluene or dmf as the reaction solvent. The starting material bromide was either commercially available,known in the literature,or prepared using the protocol in scheme B.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6-Bromo-2-methylisoindolin-1-one, its application will become more common.
Reference:
Patent; MERCK SHARP & DOHME CORP.; MSD R&D (CHINA) CO., LTD.; ACTON, John J.; BAO, Jianming; EGBERTSON, Melissa; GAO, Xiaolei; HARRISON, Scott Timothy; KNOWLES, Sandra Lee; LI, Chunsing; LO, Michael Man-Chu; MAZZOLA, Robert D., Jr.; MENG, Zhaoyang; RUDD, Michael T.; SELYUTIN, Oleg; TELLERS, David M.; TONG, Ling; WAI, Jenny Miu-Chun; (125 pag.)WO2017/107089; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem