3,5-Dimethoxypyridine synthesis
- Product Name:3,5-Dimethoxypyridine
- CAS Number:18677-48-0
- Molecular formula:C7H9NO2
- Molecular Weight:139.15
124-41-4
71902-33-5
18677-48-0
1. 3,5-difluoropyridine (5.4 g, 46.8 mmol, 1 eq.) was dissolved in methanol (45 mL). 2. Sodium methanolate (7.5 g, 140.4 mmol) was added to the above solution. 3. The reaction mixture was divided equally into three microwave reactor tubes. 4. Heat each tube separately in the microwave reactor at 135 °C for 1 hour. 5. 5. Upon completion of the reaction, the contents of the three reaction tubes were combined and concentrated. 6. The concentrate was diluted with a mixture of ethyl acetate (100 mL) and brine (30 mL). 7. The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated. 8. Redissolve the crude product in methanol (45 mL) and add sodium methanolate (7.5 g, 140.4 mmol). 9. Steps 3 through 7 were repeated. 10. Dissolve the final crude product in a mixture of ethyl acetate (200 mL) and brine (30 mL). 11. Separate the organic layer, dry with anhydrous sodium sulfate, and concentrate. 12. The product was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane as eluent to afford 3,5-dimethoxypyridine (3.73 g, 57% yield) as an off-white solid. 13. The product was confirmed by 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). 14. lRMS (M+H+) m/z 140.1.
124-41-4
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18677-48-0
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Yield:18677-48-0 91%
Reaction Conditions:
with methanol at 135; for 0.25 h;microwave;
Steps:
To a vial charged with 2,5-difluoropyridine (127 mg, 1.1 mmol) was added a 25% solution of sodium methoxide in methanol (2 mL). Upon completion of addition, the reaction mixture was heated at 135 0C under microwave conditions for 15 min. At the conclusion of this period, the reaction mixture was diluted with brine (5 mL) and extracted with EtOAc (3 x 5 mL). The combined extracts were dried over Na2SO4 and filtered. The volatiles were removed under reduced pressure to provide a residue. The residue was subjected to chromatography on silica gel eluting with 0 to 60% EtOAc/hexanes to provide Intermediate 23 as a yellow oil (139 mg, 91%). 1H NMR (400 MHz, CDCl3) δ ppm 3.80 (s, 6 H), 6.87 (t, J-2.20 Hz, 1 H), 7.78 (d, J=2.20 Hz, 2 H).
References:
BRISTOL-MYERS SQUIBB COMPANY WO2007/30582, 2007, A2 Location in patent:Page/Page column 88
124-41-4
726 suppliers
$12.00/25g
71902-33-5
169 suppliers
$6.00/1g
18677-48-0
126 suppliers
$20.00/100mg
2457-47-8
310 suppliers
$6.00/5g
18677-48-0
126 suppliers
$20.00/100mg
2457-47-8
310 suppliers
$6.00/5g
865-33-8
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18677-48-0
126 suppliers
$20.00/100mg
2457-47-8
310 suppliers
$6.00/5g
124-41-4
726 suppliers
$12.00/25g
18677-48-0
126 suppliers
$20.00/100mg