Hydrochloric Acid → 6-Aminopyridine-3-carbaldehyde

Temperature

-78 °C

To a suspension of 1 g of 6-aminopyridine-3-carbonitrile in 20 mL of toluene cooled to −78° C. are added dropwise 15 mL of a 1.2 M solution of diisobutylaluminum hydride in toluene. The reaction medium is stirred for 30 minutes at −78° C. and is then allowed to warm slowly to 20° C. After cooling again to −78° C., 6 mL of water are added slowly and the resulting mixture is stirred for 1 hour at −78° C. The reaction medium is stirred for 16 hours at 20° C., treated with 20 mL of 2.5 N hydrochloric acid, stirred for 20 minutes, basified by addition of concentrated sodium hydroxide and extracted three times with 100 mL of dichloromethane. The combined organic phases are dried and concentrated to dryness under reduced pressure. The residue is taken up in 40 mL of ethyl acetate and 40 mL of saturated sodium bisulfite solution. The aqueous phase is washed twice with 40 mL of ethyl acetate, basified to about pH 14 by addition of concentrated sodium hydroxide, and extracted three times with 50 mL of dichloromethane. The combined organic phases are dried and concentrated to dryness under reduced pressure to give 200 mg of crude 6-aminopyridine-3-carboxaldehyde in the form of a yellow powder, which is used without further purification.

1. temperatureto warm slowly to 20° C
2. temperatureAfter cooling again to −78° C.
3. stirringthe resulting mixture is stirred for 1 hour at −78° C
4. stirringThe reaction medium is stirred for 16 hours at 20° C.
5. stirringstirred for 20 minutes
6. extractionextracted three times with 100 mL of dichloromethane
7. customThe combined organic phases are dried
8. concentrationconcentrated to dryness under reduced pressure
9. washThe aqueous phase is washed twice with 40 mL of ethyl acetate
10. additionbasified to about pH 14 by addition of concentrated sodium hydroxide
11. extractionextracted three times with 50 mL of dichloromethane
12. customThe combined organic phases are dried
13. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-9c21351b964b4afdabac8a8d2e257afd

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902219B2