Carbon Dioxide → 3-Chloropyridine-4-carboxylic acid

A solution of 3-chloropyridine (1.00 mL, 10.5 mmol) in THF at −78° C. was treated dropwise with a solution of lithium diisopropylamide in THF [freshly prepared by addition of butyllithium (7.21 mL, 11.5 mmol) to diisopropylamine (11.5 mmol)]. After 0.25 h, the mixture was treated with carbon dioxide (g) and slowly warmed to ambient temperature. The mixture was concentrated, partitioned between EtOAc and water, and the aqueous layer was washed with EtOAc (2×). The pH of the aqueous layer was adjusted (˜3) by addition of 1 N HCl and then washed with EtOAc (3×). The combined extracts were dried with magnesium sulfate and concentrated. The residue was recrystallized from EtOAC yielding 200 mg (12%) of 3-chloroisonicotinic acid.

1. concentrationThe mixture was concentrated
2. custompartitioned between EtOAc and water
3. washthe aqueous layer was washed with EtOAc (2×)
4. additionby addition of 1 N HCl
5. washwashed with EtOAc (3×)
6. dry with materialThe combined extracts were dried with magnesium sulfate
7. concentrationconcentrated
8. customThe residue was recrystallized from EtOAC

ORD record

ord-f91fae37fab04653a5966c8732cd7e3b

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06716855B2