Application of 104618-31-7, These common heterocyclic compound, 104618-31-7, name is 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione, its 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 mixture of 7-bromoquinoxalin-5-ol (47.53 g, 211.2 mmol), 2-(4- hydroxycyclohexyl)isoindoline-l,3-dione (52.41 g, 213.7 mmol), and PPh3 (87.31 g, 332.9 mmol) in THF (740 mL) at 21 C was added tert-butyl (NZ)-N-tert- butoxycarbonyliminocarbamate (DTBAD) (79.51 g, 328.0 mmol) in portions over 40 min so as to maintain the temperature below 30 C and the resultant reaction mixture was stirred at room temperature for a further 20 h. The reaction was evaporated in vacuo. The residual reddish-brown viscous oil was dissolved in CH2C12 and filtered through a plug of silica in a glass column using applied air pressure (plug was made with 1L of dry silica suspended in CH2C12). The plug was eluted with CH2C12, the fractions were combined and evaporated in vacuo to afford a red-brown viscous oil/foam, that was then dissolved in 700 mL of MeOH before precipitating. The mixture was stirred at room temperature for 1 h, filtered, washed with cold MeOH (500 mL) and Et20 (100 mL), then dried in vacuo to yield a tan solid that was suspended in 300 mL MeOH and brought to reflux for 10 min. The suspension was cooled to room temperature and filtered, washed with a further MeOH and Et20 (4: 1), and dried in vacuo to provide 2-[4-(7- bromoquinoxalin-5-yl)oxycyclohexyl]isoindoline-l,3-dione (58.43 g, 126.6 mmol, 59.94%). 1H NMR (400 MHz, CDC13) d 8.96 (d, J = 1.8 Hz, 1H), 8.86 (d, J = 1.8 Hz, 1H), 7.91 (d, J = 1.9 Hz, 1H), 7.89 – 7.82 (m, 2H), 7.78 – 7.67 (m, 2H), 7.30 (d, J = 1.9 Hz, 1H), 4.95 (s, 1H), 4.29 (tt, J = 12.5, 3.7 Hz, 1H), 2.87 (qd, J = 13.1, 3.5 Hz, 2H), 2.44 (d, J = 15.2 Hz, 2H), 1.80 (t, J = 14.1 Hz, 2H), 1.67 (d, 2H). ESI-MS m/z calc. 451.05316, found 452.19 (M+l)+; Retention time: 0.92 minutes.
Statistics shows that 2-(4-Hydroxycyclohexyl)isoindoline-1,3-dione is playing an increasingly important role. we look forward to future research findings about 104618-31-7.
Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WEINBERG, Marc, Saul; D’ASTOLFO, Diego, Sebastian; MAHAJAN, Sudipta; (258 pag.)WO2019/143675; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem