4-Aminopyridine → N-(2,2-Diethoxyethyl)pyridin-4-amine

Temperature

50 °C

A solution of 4-aminopyridine (23.2 g.) in a mixture of dried hexamethylphosphoric triamide (45 g.) and dried dimethylformamide (80 ml) was dropwise added over 20 minutes with stirring and ice-cooling to a suspension of 65.5% sodium hydride (10 g.) in dried dimethylformamide (20 ml.). After dried dimethylformamide (20 ml.) was further added thereto, the mixture was stirred for 1 hour under ice-cooling, for 20 minutes at ambient temperature and for 40 minutes at 50° C. A solution of bromoacetaldehyde diethyl acetal (54 g.) in dried dimethylformamide (20 ml.) was dropwise added thereto over 5 minutes at 50° C. The resulting mixture was stirred for 15 hours at 80° C and for 3 hours at 100° C. After cooling, water was added to the reaction mixture and the resulting mixture was concentrated under reduced pressure to remove dimethylformamide. To the residue was added water and the mixture was extracted with ethyl acetate. The extract was in turn washed 3 times with water and once with a saturated sodium chloride aqueous solution and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the residual oil was purified by column chromatography on alumina (300 g.) using a mixture of ethyl acetate and hexane (1 : 1) as a developing solvent to give oil of 4-pyridylaminoacetaldehyde diethyl acetal (7.0 g.).

1. additionwas dropwise added over 20 minutes
2. stirringthe mixture was stirred for 1 hour under ice-
3. stirringThe resulting mixture was stirred for 15 hours at 80° C and for 3 hours at 100° C
4. temperatureAfter cooling
5. concentrationthe resulting mixture was concentrated under reduced pressure
6. customto remove dimethylformamide
7. additionTo the residue was added water
8. extractionthe mixture was extracted with ethyl acetate
9. washwashed 3 times with water
10. dry with materialonce with a saturated sodium chloride aqueous solution and dried over magnesium sulfate
11. distillationThe solvent was distilled off under reduced pressure
12. customthe residual oil was purified by column chromatography on alumina (300 g.)
13. additiona mixture of ethyl acetate and hexane (1 : 1) as a developing solvent

ORD record

ord-5fa1db5a58f44ca89c8211210473058a

Source dataset

uspto-grants-1978_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04096263