Dichloromethane → HCID 58317545, compound

A 22-L 3-neck RBF equipped with overhead stirrer, refluxing condenser, and N2 inlet/outlet, and having all glass or PTFE-coated parts, was sequentially charged with 4,6-dichloro-7-fluoro-1-hydroxy-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (908 g), DCM (4.55 L), and TFA (3.46 L, 11.76 eq). Agitation was started and Et3SiH (3.05 L, 4.97 eq) was added. The cloudy mixture was heated to reflux, resulting in a clear solution that was stirred at refluxing conditions for 24 h. The mixture was cooled to RT and stirred overnight. The orange solution was cooled to <10° C. using an ice bath. Methyl tert-butyl ether (14.0 L) was added via a peristaltic pump within a 1 h period. The resultant slurry was stirred at <10° C. for 1 h and then filtered through a coarse fitted glass funnel. The filter cake was washed with MTBE (2×4 L). The solid was dried under high vacuum at RT for 19 h to afford the title compound (802 g, 94%). 1H NMR (500 MHz, DMSO-d6) δ ppm 4.55 (s, 2H), 9.15 (s, 1H). [M+H] calc'd for C7H3Cl2FN2O, 221. found, 221.

1. customA 22-L 3-neck RBF equipped with overhead stirrer
2. temperaturerefluxing condenser, and N2 inlet/outlet
3. temperatureThe cloudy mixture was heated
4. temperatureto reflux
5. customresulting in a clear solution that
6. temperatureat refluxing conditions for 24 h
7. stirringstirred overnight
8. temperatureThe orange solution was cooled to <10° C.
9. stirringThe resultant slurry was stirred at <10° C. for 1 h
10. filtrationfiltered through
11. customa coarse fitted glass funnel
12. washThe filter cake was washed with MTBE (2×4 L)
13. customThe solid was dried under high vacuum at RT for 19 h

ORD record

ord-960fbd00152f4705bbcc8bda2e944c39

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181255B2