Hydrochloric Acid → 6,11-Dihydro-5H-dipyrido[2,3-b:3',4'-f]azepin-5-ol

Temperature

-78 °C

2-(4-Aminopyridin-3-yl)-1-(2-fluoropyridin-3-yl)ethanol (6.00 mmol, Intermediate D-4) was dissolved in THF (200 mL) under an atmosphere of nitrogen. The solution was cooled to −78° C., then a solution of potassium tert-butoxide (36.0 mL, 1.0 M in THF, 36.0 mmol) was added dropwise. The mixture turned orange/red, then became darker brown. After the addition, the mixture was slowly warmed to 0° C. After stirring for 3 hours at 0° C., the reaction mixture was poured into a cold solution of saturated NaCl/water and HCl (2.0 mL, 12 M, 24 mmol) and stirred (pH ˜13) and then extracted 3× with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude product was adsorbed onto silica gel and then chromatographed on silica gel eluting with 10% methanol/CH2Cl2 to give the desired product as a white solid (1.15 g, 89%).

1. additionAfter the addition
2. temperaturethe mixture was slowly warmed to 0° C
3. stirringstirred (pH ˜13)
4. extractionextracted 3× with ethyl acetate
5. washThe combined extracts were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customchromatographed on silica gel eluting with 10% methanol/CH2Cl2

ORD record

ord-c3a30b20b12d47c3b93d2fc688e95bd3

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835423B2