Boron trifluoride etherate → 5-Acetoxy-2-methoxypyridine

To 47.6 mL of boron trifluoride etherate (387 mmol, Aldrich) cooled to −10° C. under N2 was added 24 g (193 mmol, Aldrich)) of 5-amino-2-methoxypyridine dissolved in 100 mL of dimethoxyethane. Then tert-butyl nitrite (20.2 mL, 193 mmol, Aldrich) was added at a rate which kept the temperature below 0° C. After 1 hour at −10° C. pentane (400 mL) was then added to the reaction mixture, the pentane solution was decanted, and the residue was washed with cold ether and dissolved in 200 mL of acetic anhydride. The resulting solution was heated to 100° C.±5° C. for 1 hour. The solvent was removed under vacuum, and the residue was suspended in saturated aqueous Na2CO3(200 mL) and extracted with ethyl ether (3×200 mL). The ether solution was dried (MgSO4), the solvent was removed in vacuo, and the residue was chromatographed on silica gel, eluting with 95:5 to 80:20 hexane:ethyl acetate to give 7.3 (20.7%) g of the title compound. MS (CI/NH3) m/e: 168 (M+H)+, 185 (M+NH4)+. 1H NMR (CDCl3 300 MHz) δ.2.30 (s, 3H), 3.92 (s, 3H), 6.75 (d, J=9.0 Hz 1H), 7.35 (dd, J=2.5,9.0 1H), 7.95 (d, J=3.0 Hz 1H). Anal. calcd. for C8H9NO3 C, 57.48; H, 5.43; N, 8.38. Found: C, 57.46; H, 5.40; N, 7.99.

1. customthe temperature below 0° C
2. customthe pentane solution was decanted
3. washthe residue was washed with cold ether
4. dissolutiondissolved in 200 mL of acetic anhydride
5. temperatureThe resulting solution was heated to 100° C.±5° C. for 1 hour
6. customThe solvent was removed under vacuum
7. extractionextracted with ethyl ether (3×200 mL)
8. dry with materialThe ether solution was dried (MgSO4)
9. customthe solvent was removed in vacuo
10. customthe residue was chromatographed on silica gel
11. washeluting with 95:5 to 80:20 hexane

ORD record

ord-2d27f7441bea455ca04782381f993b7b

Source dataset

uspto-grants-2002_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06403575B1