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 5-amino-2-bromopyridine from step 128a above dissolved in 35 mL of DME. Then tert-butyl nitrite (14.7 mL, 125 mmol, Aldrich) was added at a rate which kept the temperature below 0° C. DME (65 mL) and methylene chloride (60 mL) were then added. After 10 minutes at -10° C. the mixture was warmed to 5° C. and stirred for 30 min. 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 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 2.35 (s, 3H) 7.37 (dd, 1H), 7.51 (d, 1H), 8.19-8.21 (d, 1H) MS m/z: 216 (M+H)+, 233 (M+NH4)+.

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

ORD record

ord-92941e0143cc414886ed0e9afa6afb33

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06133253