Methanol → 3,5-Dimethoxypyridine

Temperature

135 °C

To a solution of 3,5-difluoropyridine (5.4 g, 46.8 mmol, 1 eq.) in MeOH (45 mL) was added NaOMe (7.5 g, 140.4 mmol). The mixture was divided into three microwave tubes and individually heated at 135° C. for 1 h in a microwave reactor. The three tubes were combined, concentrated, and diluted with a mixture EtOAc (100 mL) and brine (30 mL). The organic layer was dried over Na2SO4 and concentrated. The crude was re-dissolved in MeOH (45 mL) and added NaOMe (7.5 g, 140.4 mmol). The mixture was again divided into three microwave tubes and individually heated at 135° C. for 1 h in a microwave reactor. The three tubes were combined and concentrated. The crude was dissolved in a mixture of EtOAc (200 mL) and brine (30 mL). The organic layer was dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 3,5-dimethoxypyridine (3.73 g, 57%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J=2.4 Hz, 2H), 6.76 (t, J=2.4 Hz, 1H), 3.88 (s, 6H). LRMS (M+H+) m/z 140.1.

1. concentrationconcentrated
2. additiondiluted with a mixture EtOAc (100 mL) and brine (30 mL)
3. dry with materialThe organic layer was dried over Na2SO4
4. concentrationconcentrated
5. dissolutionThe crude was re-dissolved in MeOH (45 mL)
6. temperatureindividually heated at 135° C. for 1 h in a microwave reactor
7. concentrationconcentrated
8. dissolutionThe crude was dissolved in a mixture of EtOAc (200 mL) and brine (30 mL)
9. dry with materialThe organic layer was dried over Na2SO4
10. concentrationconcentrated
11. custompurified on silica gel using
12. additiona mixture of EtOAc and hexanes as eluent

ORD record

ord-f2c2a27df6b14aec80f7ac3667d8b391

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012450B2