Nitric Acid → HCID 178496287, compound

Temperature

-6 °C

4-Aminopyridine (3.6 g, 38 mmol) was added to a mixture of phosphoric acid (10 mL, 150 mmol) and nitric acid (5 mL, 78 mmol) at −6° C. Sodium nitrite (3.2 g, 46 mmol) was added portionwise to the mixture at −6° C., and then crushed ice (ca. 25 g) was added into the solution. After stirring at −6° C. for 10 min, the mixture was poured into a suspension of methyl 4-methoxyacetoacetate (5.0 mL, 38 mmol) and sodium acetate (44 g, 540 mmol) in MeOH (100 mL) at 0° C. The mixture was partitioned between AcOEt and water. The aqueous layer was extracted with AcOEt. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residual solid was washed with AcOEt/hexane (1/3) to give the title compound (1.8 g, 19% yield) as a yellow solid: 1H NMR (300 MHz, CDCl3): δ ppm 3.48-3.53 (3H, m), 3.89-3.95 (3H, m), 4.64-4.69 (2H, m), 7.17-7.34 (2H, m), 8.54-8.60 (2H, m), 12.65 (1H, brs).

1. customThe mixture was partitioned between AcOEt and water
2. extractionThe aqueous layer was extracted with AcOEt
3. extractionThe combined organic extract
4. washwas washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. washThe residual solid was washed with AcOEt/hexane (1/3)

ORD record

ord-cfa8fffa68ac473c964071c1e3580257

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778944B2