Hydrochloric Acid → HCID 58317608, compound

To a butyllithium-hexane solution (100 mL, 160 mmol) in THF (200 mL) was slowly added diisopropylamine (27.4 mL, 192 mmol) in THF (15 mL) at −78° C. The mixture was stirred at the same temperature for 15 min. A solution of 2,6-dichloro-5-fluoronicotinic acid (14.98 g, 71.4 mmol) in THF (15 mL) was added and the mixture was stirred for 2 h. Next, DMF (29.3 mL, 378 mmol) was added and the mixture was stirred for 1 h. Hydrochloric acid (1N, 400 mL) was added and the mixture was subsequently extracted with EtOAc (2×300 mL). The organic phase was basified with saturated aq NaHCO3 solution and the aqueous phase was separated. The aqueous phase was re-acidified with 1N HCl (300 mL) and extracted with EtOAc (2×300 mL). The organic phase was washed with H2O (200 mL) and brine (200 mL), dried over MgSO4, and evaporated. The residue was washed with Hexane/EtOAc (1/8) to give the title compound as a white solid (11.5 g, 67.7%). 1H NMR (500 MHz, DMSO-d6) δ ppm 6.85 (br s, 1H), 8.82 (br s, 1H).

1. customat −78° C
2. stirringthe mixture was stirred for 2 h
3. stirringthe mixture was stirred for 1 h
4. extractionthe mixture was subsequently extracted with EtOAc (2×300 mL)
5. customthe aqueous phase was separated
6. extractionextracted with EtOAc (2×300 mL)
7. washThe organic phase was washed with H2O (200 mL) and brine (200 mL)
8. dry with materialdried over MgSO4
9. customevaporated
10. washThe residue was washed with Hexane/EtOAc (1/8)

ORD record

ord-f5244fb78a804019b16dcc9b19b8bb20

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181255B2