Carbon Dioxide → 2,5-Dibromopyridine-4-carboxylic acid

Temperature

-30 °C

A 20-L 4-necked round-bottom flask purged and maintained under a N2 atmosphere was charged with a solution of diisopropylamine (582 g, 5.76 mol, 1.05 equiv) in THF (4.2 L), followed by the dropwise addition over 30 min of n-BuLi (2.4 M, 2.4 L, 1.05 equiv) with stirring at −30° C. The resulting solution was stirred at −30° C. for 30 min then cooled to −80° C. To the LDA solution was added dropwise over 1 h with stirring a solution of 2,5-dibromopyridine (1.3 Kg, 5.49 mol, 1.00 equiv) in THF (5.2 L). The resulting solution was stirred at −70° C. for 30 min. To the mixture was added CO2 (dry ice) (1267 g, 28.80 mol, 5.00 equiv) in several batches at −70° C. The resulting solution was stirred at −70° C. for 30 min, quenched by the addition of 5 L of water at −70° C., concentrated in vacuo and extracted with 3×4 L of EtOAc. The pH value of the aqueous layer was adjusted to 3-4 with HCl (12 mol/L). The precipitate was collected by filtration to afford 2,5-dibromoisonicotinic acid (A-2) white solid.

1. customA 20-L 4-necked round-bottom flask purged
2. temperaturemaintained under a N2 atmosphere
3. stirringThe resulting solution was stirred at −30° C. for 30 min
4. temperaturethen cooled to −80° C
5. stirringThe resulting solution was stirred at −70° C. for 30 min
6. stirringThe resulting solution was stirred at −70° C. for 30 min
7. customquenched by the addition of 5 L of water at −70° C.
8. concentrationconcentrated in vacuo
9. extractionextracted with 3×4 L of EtOAc
10. filtrationThe precipitate was collected by filtration

ORD record

ord-d453a21dbb8d43098a6ea7520cebb204

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388171B2