Carbon Dioxide → 3,5-Dichloropyrazine-2-carboxylic acid

Temperature

-78 °C

To a solution of lithium diisopropylamide (2.0 M heptane/tetrahydrofuran/ethylbenzene, 11.10 mL, 22.20 mmol) in THF (75 mL) at −78° C. was added a solution of 2,6-dichloropyrazine (1.44 g, 9.67 mmol) in THF (20 mL) at room temperature over 20 min. The reaction mixture was stirred at −78° C. for 1.5 h and added via cannula to a 3-neck flask containing dry ice at −78° C. The reaction mixture was warmed from −78° C. to room temperature over 21 h and quenched with 5 M HCl. The mixture was partitioned between brine and EtOAc. The aqueous phase was acidified to pH 3.5 with 5 M HCl. The aqueous phase was extracted with EtOAc (6×) and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (5% to 10% MeOH in DCM) gave 3,5-dichloropyrazine-2-carboxylic acid (0.408 g, 2.11 mmol, 22% yield) as a light brown solid. LC/MS (ESI+) m/z=193.0 (M+H)+.

1. additionadded via cannula to a 3-neck flask
2. temperatureThe reaction mixture was warmed from −78° C. to room temperature over 21 h
3. customquenched with 5 M HCl
4. customThe mixture was partitioned between brine and EtOAc
5. extractionThe aqueous phase was extracted with EtOAc (6×)
6. washthe combined organic extracts were washed with brine (1×)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by flash column chromatography on silica gel (5% to 10% MeOH in DCM)

ORD record

ord-473d751f8afd43c5a5152e6e44b4b27d

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085576B2