Toluene → HCID 71270645, compound

In a 1 L round bottom flask, N,N-diisopropylethylamine (15.2 mL, 0.0871 mol) was added to a suspension of (1S,2R)-1-amino-5-chloroindan-2-ol (16.0 g, 0.0871 mol) and phthalic anhydride (14.2 g, 0.0958 mol) in toluene (473 mL, 4.44 mol), and the reaction mixture was heated at reflux for 18 hours. The reaction was cooled to room temperature, at which point a large amount of solid precipitated. The solid, which was the desired product, was filtered, rinsed with EtOAc and collected. The filtrate was cooled to 0° C., filtered and the solid was rinsed with EtOAc and combined with the first batch. The filtrate was transferred to a separatory funnel and diluted with H2O (200 mL). The layers were separated, and the aqueous layer was extracted EtOAc (3×200 mL). The combined organic layers were washed 1× brine (100 mL), dried over MgSO4, filtered, and concentrated in vacuo. The resulting off-white solid was suspended in EtOAc, the large chunks were broken up with sonication, and the suspension was cooled to 0° C. The solid was filtered and combined with the previous 2 batches. The filtrate was concentrated in vacuo, and the resultant white solid was suspended one final time in Et2O (100 mL), filtered and combined with the previous 3 batches. The total yield of all four batches of solid was 25.3 g (92%). LCMS: (FA) ES+ molecular ion 314, major ionization 167; 1H NMR (400 MHz, DMSO) δ 7.83 (s, 4H), 7.33 (s, 1H), 7.27 (d, J=8.2, 1H), 7.19 (dd, J=2.0, 8.1, 1H), 5.52 (d, J=7.4, 1H), 5.34 (d, J=5.2, 1H), 4.64 (dt, J=6.9, 12.7, 1H), 3.21 (dd, J=7.4, 16.1, 1H), 3.02 (dd, J=6.1, 16.1, 1H).

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 18 hours
3. customprecipitated
4. filtrationwas filtered
5. washrinsed with EtOAc
6. customcollected
7. temperatureThe filtrate was cooled to 0° C.
8. filtrationfiltered
9. washthe solid was rinsed with EtOAc
10. customThe filtrate was transferred to a separatory funnel
11. additiondiluted with H2O (200 mL)
12. customThe layers were separated
13. extractionthe aqueous layer was extracted EtOAc (3×200 mL)
14. washThe combined organic layers were washed 1× brine (100 mL)
15. dry with materialdried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. customthe large chunks were broken up with sonication
19. temperaturethe suspension was cooled to 0° C
20. filtrationThe solid was filtered
21. concentrationThe filtrate was concentrated in vacuo
22. filtrationfiltered

ORD record

ord-05b8855d45144ed1a57c7bc7e53cd753

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809356B2