Tetrahydrofuran → 6-Methoxypyridine-3-carbaldehyde

HRID 705989Notes

Reaction equation

HRID 705989 reaction equation
[Li+].CCC[CH2-].Br[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=1.C1C[O:18][CH2:17]C1>>[CH3:14][O:13][C:10]1[N:11]=[CH:12][C:7]([CH:17]=[O:18])=[CH:8][CH:9]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 61028n-Butyl lithiumHCID 27348955-Bromo-2-methoxypyridine

Product 1

HCID 33645766-Methoxypyridine-3-carbaldehydeYield 71.2%

Conditions

Temperature
-78 °C

Procedure

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 coloumn and cyclohexane/EtOAc solvent system (gradient 1-10% of EtOAc in 20 coloumn 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)

Workup

  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

Sources & evidence

ORD record
ord-9fe2be75a1af4b4cae6df8225c4632d4
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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