Hydrochloric Acid → 1H-Pyrrolo(2,3-b)pyridine

Temperature

-15 °C

To a stirred solution of 2-(tert-butoxycarbonylamino)-3-methylpyridine (Example 2a) (100 g) in anhydrous tetrahydrofuran and cooled to -15° C. was slowly added hexyllithium (2.8M, 350 ml) over 40 minutes, while maintaining the reaction temperature at -15° C. The reaction mixture was aged at -15° C. for 15 minutes and then allowed to warm to -5° C. Anhydrous dimethylformamide (40 ml) was added in one portion (temp. to 5° C.) and the resulting yellow suspension vigorously stirred at ambient temperature for 30 minutes. 5.5M Hydrochloric acid (900 ml) was added in one portion and the mixture heated at 45° C. for one hour. The mixture was cooled to 20° C. and the phases separated. The aqueous phase was covered with isopropyl acetate (500 ml), cooled to 5° C. and with vigorous stirring, neutralised by the addition of sodium hydroxide pellets (200 g, 5.0 mole). The phases were separated and the aqueous phase extracted with isopropyl acetate (500 ml). The organic phases were combined, washed with 2%w/w sodium metabisulphite (2×500 ml) and evaporated to residue (56.8 g, 91%w/w purity, 91%w/w assay yield (method 1)).

1. customover 40 minutes
2. temperatureto warm to -5° C
3. temperaturethe mixture heated at 45° C. for one hour
4. temperatureThe mixture was cooled to 20° C.
5. customthe phases separated
6. temperaturecooled to 5° C. and with vigorous stirring
7. additionneutralised by the addition of sodium hydroxide pellets (200 g, 5.0 mole)
8. customThe phases were separated
9. extractionthe aqueous phase extracted with isopropyl acetate (500 ml)
10. washwashed with 2%w/w sodium metabisulphite (2×500 ml)
11. customevaporated to residue (56.8 g, 91%w/w purity, 91%w/w assay yield (method 1))

ORD record

ord-0650061d5e554f6d8f6f0ad86f986dce

Source dataset

uspto-grants-1997_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05681959