Carbon Dioxide → 3,5-Dimethoxyisonicotinic acid

Temperature

-78 °C

A solution of 3,5-dimethoxypyridine (600 mg, 4.3 mmol) (prepared according to the method of Testaferri, L. et al Tetrahedron, 1985, 41, 1373) in THF (2.6 ml) was added to a solution of LDA [generated from n-BuLi (1.9 ml, 2.5 M in hexane, 4.73 mmol) and diisopropylamine (0.6 ml, 5.16 mmol)] in THF (2.6 ml) at −78° C. under nitrogen. The reaction mixture was stirred for 30 minutes at −78° C., transferred via cannula to a suspension of crushed solid CO2 (30 g) in toluene (100 ml) under vigorous stirring and warmed to room temperature. The reaction is quenched by addition of water (20 ml) to and 1M NaOH (10 ml) and the aqueous layer separated, acidified to pH 4 with glacial acetic acid and extracted with 10% MeOH in dichloromethane (3×50 ml). The combined organic layers were dried (MgSO4) and the solvent removed under vacuum to give the title compound (502 mg, 63%) as a white solid.

1. stirringunder vigorous stirring
2. temperaturewarmed to room temperature
3. customThe reaction is quenched by addition of water (20 ml) to and 1M NaOH (10 ml)
4. customthe aqueous layer separated
5. extractionextracted with 10% MeOH in dichloromethane (3×50 ml)
6. dry with materialThe combined organic layers were dried (MgSO4)
7. customthe solvent removed under vacuum

ORD record

ord-a2f67cd809f94f05b072e490f8eab7a4

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07253171B2