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 923590-95-8 as follows. Application In Synthesis of 4-Bromoisoindoline hydrochloride
3. Kumada Coupling of Bromo-Iso-Indole [0258] bromoisoindoline HCl salt (25 g, 106.6 mmol), Pd(OAc)2 (0.199 g, 0.533 mmol), and the ligand (di-tert-butylneopentylphosphonium tetrafluoroborate, 0.325 g, 1.066 mmol). PhMe (toluene) (450 mL, de-oxygenated via sparging with N2) was then added, and the resulting slurry was then cooled to Ti=5 C. using an external bath. Allylmagnesium chloride (1.7 N in THF, 207 mL, 351.8 mmol) was charged to an addition funnel via cannula, and then added at a rate such that Ti<20 C. The resulting solution was then was heated to Ti=45-50 C. [0260] After 16 hours, LC showed >99% conversion of starting material. The reaction was cooled to room temperature, and then was inverse-quenched into 250 mL of 15% aqueous citric acid. The phases were separated, and the aqueous phase containing the product was held while the dark organic phase was rejected. The extractor that contained the aqueous phase was charged with 125 mL of PhMe. The pH of the aqueous phase was adjusted by the addition of 115 mL of NH4OH. The phases were separated, and the organic phase containing the product was held while the aqueous phase was rejected. The organic phase was washed with 20 mL of 15% aqueous NaCl. The PhMe solution was concentrated with azeotrope to a 10 volume solution (KF<2000 ppm H2O). [0261] This PhMe solution of product was transferred to 250 mL flask with overhead stirring. An addition funnel was charged with 17.5 mL of 5.33 M HCl in IPA (5.3 M), which was added slowly over 20 minutes. The resulting slurry was aged for 30 minutes at Ti=40 C., and then was gradually cooled to Ti=20-22 C. over 30 minutes. After aging for 1 hour, the slurry was slowly cooled to Ti=0 C. over 30 minutes by use of an external bath. After 30 minutes, the slurry was filtered. The cake was washed with 16 mL of cold (Ti=-10 vC) 14:2 PhMe:IPA. The cake was then washed with 15 mL of ambient temperature (Ti=22 C.) MTBE. After drying, 7.6 g of allyl isoindoline was isolated as an off white solid. The isolated product assayed for 98.7 wt %.
According to the analysis of related databases, 923590-95-8, the application of this compound in the production field has become more and more popular.
Reference:
Patent; Chen, Cheng; Kong, Jongrock; Humphrey, Guy; Dolman, Sarah; Li, Hongmei; Tudge, Matthew T.; Yong, Kelvin; Xiang, Bangping; Zacuto, Michael; US2013/274463; (2013); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem