Acetic Acid → HCID 178448378, compound

Temperature

-20 °C

To a solution of Boc-NVA-OH (4.5 g, 21 mmol) in acetonitrile (68 mL) and 4-methylmorpholine (2.41 mL, 21.9 mmol) cooled to −20° C. was added isobutyl chloroformate (2.7 mL, 21 mmol) dropwise. The mixture was stirred for 120 minutes at −20° C. and then 4-bromo-1,2-benzenediamine (3.87 g, 20.7 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 18 hours. The solvent was evaporated, redissolved in ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The resulting residue was dissolved in acetic acid (20 mL, 400 mmol) and stirred at 70° C. for 6 hours. The acetic acid was removed in vacuo and the mixture was redissolved in ethyl acetate, washed with saturated aqueous solution of sodium hydrogen carbonate, and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The resulting oil was redissolved in dichloromethane, treated with activated carbon and filtered through a plug of celite. Purification by silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the title compound (5.95 g, 78%) as a white solid.

1. temperatureto warm to room temperature
2. stirringstirred for 18 hours
3. customThe solvent was evaporated
4. dissolutionredissolved in ethyl acetate
5. washwashed with water, saturated aqueous solution of sodium hydrogen carbonate, and brine
6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. stirringstirred at 70° C. for 6 hours
10. customThe acetic acid was removed in vacuo
11. dissolutionthe mixture was redissolved in ethyl acetate
12. washwashed with saturated aqueous solution of sodium hydrogen carbonate, and brine
13. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. dissolutionThe resulting oil was redissolved in dichloromethane
17. additiontreated with activated carbon
18. filtrationfiltered through a plug of celite
19. customPurification by silica gel column chromatography
20. washeluting with a 0-100% ethyl acetate/hexanes gradient

ORD record

ord-3d3d52de516f4a1b9d2b480054513460

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927587B2