Hydrochloric Acid → HCID 58317608, compound

To a solution of diisopropylamine (96 g, 0.94 mol) in THF (800 mL) was slowly added n-butyllithium (379 mL, 0.95 mol, 2.5 M) at −78° C. The mixture was stirred at the same temperature for 30 minutes. To the mixture was added 2,6-dichloro-5-fluoronicotinic acid (90 g, 0.43 mol) in THF (500 mL). The solution was stirred for an additional 2 h. To the mixture was added DMF (154 mL, 1.94 mol) dropwise, The mixture was stirred for 1 h, after which 2N HCl (1.54 L) (pH<1) was introduced. The mixture was subsequently extracted with EtOAc and the organic layers were basified with aqueous NaHCO3 (pH>8). The aqueous layer was separated, acidified with 2N HCl (1.2 L) (pH<1), and extracted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was washed with DCM to give the title compound as a reddish solid (81.6 g, 80%). 1H NMR (DMSO-d6, 400 MHz) δ ppm 6.85 (s, 1H), 8.83 (s, 1H). [M+H] calc'd for C7H2C12FNO3, 238. found, 238.

1. customat −78° C
2. stirringThe solution was stirred for an additional 2 h
3. stirringThe mixture was stirred for 1 h
4. extractionThe mixture was subsequently extracted with EtOAc
5. customThe aqueous layer was separated
6. extractionextracted with EtOAc
7. washThe organic layer was washed with water and brine
8. dry with materialdried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. washthe resulting residue was washed with DCM

ORD record

ord-b86604a7fb7a499f8cf082cd1b98ef4c

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056873B2