Dichloromethane → 3-Pyridinol, 6-bromo-, 3-acetate

Temperature

5 °C

To 25.6 mL of boron trifluoride etherate (208 mmol, Aldrich) cooled to -15° C. under N2 was added 18 g (104 mmol) of 3-amino-6-bromopyridine (from Step 123a above) dissolved in 35 mL of dimethoxyethane. Then t-Butyl nitrite (14.7 mL, 125 mmol, Aldrich) was added at a rate which kept the temperature below 0° C. Dimethoxyethane (65 mL) and methylene chloride (60 mL) were then added to aid stirring. After 10 minutes at -10° C. the mixture was allowed to warm to 5° C. and stirred for 30 minutes. Pentane (400 mL) was then added to the reaction mixture, the solid was collected by suction filtration, washed with cold ether, air dried, and dissolved in 125 mL of acetic anhydride. The resulting solution was heated to 100° C.±5° C. for 1 hour. The solvent was removed in vacuo, and the residue was suspended in saturated aqueous Na2CO3, and extracted with ethyl ether. The ether solution was dried over MgSO4, the solvent was removed in vacuo, and the residue was chromatographed on silica gel, eluting with 100:0 to 60:40 hexane:ethyl acetate to give 13.6 g of the title compound: 1H NMR (CDCl3 300 MHz) δ 8.20 (m, 1H).7.51 (d, J=8.5 Hz 1H),7.38 (dd, J=2.9, 7.5 Hz, 1H), 2.35 (s, 3H). MS (CI/NH3) m/e: 216 (M+H)+, 233 (M+NH4)+.

1. customthe temperature below 0° C
2. stirringstirred for 30 minutes
3. filtrationthe solid was collected by suction filtration
4. washwashed with cold ether, air
5. customdried
6. dissolutiondissolved in 125 mL of acetic anhydride
7. temperatureThe resulting solution was heated to 100° C.±5° C. for 1 hour
8. customThe solvent was removed in vacuo
9. extractionextracted with ethyl ether
10. dry with materialThe ether solution was dried over MgSO4
11. customthe solvent was removed in vacuo
12. customthe residue was chromatographed on silica gel
13. washeluting with 100:0 to 60:40 hexane

ORD record

ord-e6d57bfe19d64fcf80b986d12af66b46

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06133253