Carbon Dioxide → 2-[Bis(cyclopropylmethyl)amino]-6-fluoropyridine-3-carbaldehyde

Temperature

-78 °C

Diisopropylamine (1.4 mL, 9.6 mmol) was stirred in ether (10 mL). The solution is cooled −78° C. with dry ice and acetone. n-Butyllithium (4 mL, 9.6 mmol) was added and the resulting solution was allowed to stir at −78° C. for about 15 minutes. 2,6-Difluoropyridine (0.8 mL, 8.7 mmol) was added and the solution was allowed to stir at −78° C. for about 2 hours. N,N-bis-cyclopropylmethyl formamide (1.71 g, 10.9 mmol) was added and the solution was allowed to stir at −78° C. for about 1 hour. The solution was quenched with 10% potassium phosphate. The solution was extracted with ether (2×20 mL). The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and then concentrated under vacuum to give an orange oily product. Purification by silica gel chromatography and eluting with 20% ethyl acetate in hexanes afforded the title compound as an orange oil (224 mg, yield: 10.3%).

1. stirringto stir at −78° C. for about 2 hours
2. stirringto stir at −78° C. for about 1 hour
3. customThe solution was quenched with 10% potassium phosphate
4. extractionThe solution was extracted with ether (2×20 mL)
5. washThe combined organic layers were washed with water and brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. customto give an orange oily product
10. customPurification by silica gel chromatography
11. washeluting with 20% ethyl acetate in hexanes

ORD record

ord-2221056a7c924c119bec7f0704aa84a0

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604055B2