Tetrahydrofuran → 6-Methoxypyridine-3-carbaldehyde

Temperature

-78 °C

N-butyllithium, 1.6 M solution in hexanes (1.05 eq, 7.0 ml) was added dropwise to a solution of 5-bromo-2-methoxy-pyridine (2 g, 10.63 mmol) in THF, Acros dry (25 ml) under argon atmosphere at −78° C. After complete addition the mixture was stirred for another 90 minutes at −78° C. at which time DMF, acros dry (2 eq, 1.65 ml) was added dropwise. The mixture was then stirred at −78° C. for another 90 minutes. The mixture was then warmed-up to room temperature and poured into 150 ml of NaHCO3 saturated water solution. The organics were extracted with 3×70 ml of diethyl ether. The gathered ether layers were dried over Na2SO4 the solvent was evaporated and the obtained crude was purified by chromatography on BIOTAGE SP1 purification device using 25 g normal phase silica SNAP column and cyclohexane/EtOAc solvent system (gradient 1-10% of EtOAc in 20 column volumes) Solvent from the gathered fractions of appropriate composition was evaporated and obtained was 6-methoxy-pyridine-3-carbaldehyde (1.04 g, yield=71.2%, purity=95%) in form of white crystals. MS: [M+H]+=138.09 1H NMR (300 MHz; CDCl3) δ/ppm 4.04 (s, 3H), 6.85 (d, J=8.70 Hz, 1H), 8.07 (dd, J=8.70 Hz, J=2.34 Hz, 1H), 8.64 (d, J=2.34 Hz, 1H), 9.96 (s, 1H)

1. customdry (25 ml) under argon atmosphere at −78° C
2. additionAfter complete addition the mixture
3. customacros dry (2 eq, 1.65 ml)
4. additionwas added dropwise
5. stirringThe mixture was then stirred at −78° C. for another 90 minutes
6. temperatureThe mixture was then warmed-up to room temperature
7. additionpoured into 150 ml of NaHCO3 saturated water solution
8. extractionThe organics were extracted with 3×70 ml of diethyl ether
9. dry with materialThe gathered ether layers were dried over Na2SO4 the solvent
10. customwas evaporated
11. customthe obtained crude
12. customwas purified by chromatography on BIOTAGE SP1 purification device
13. customwas evaporated
14. customobtained

ORD record

ord-1f6b624ad5b64a6e8dc8487fedbed0ad

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637536B2