Potassium Carbonate → 4-ethyl-8-methoxy-1H-pyrano[3,4-c]pyridine

HRID 2396391Notes

Reaction equation

HRID 2396391 reaction equation
[CH:1](=[C:3]1[C:12]2[C:7](=[C:8]([O:13][CH3:14])[N:9]=[CH:10][CH:11]=2)[CH2:6][O:5][CH2:4]1)[CH3:2].C(=O)([O-])[O-].[K+].[K+]>C(O)CC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[CH2:1]([C:3]1[C:12]2[C:7](=[C:8]([O:13][CH3:14])[N:9]=[CH:10][CH:11]=2)[CH2:6][O:5][CH:4]=1)[CH3:2]

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 540824384-ethylidene-8-methoxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine

Product 1

HCID 106315694-ethyl-8-methoxy-1H-pyrano[3,4-c]pyridine

Reagents, catalysts & solvents 2

HCID 84599Chlorotris(triphenylphosphine)rhodium(I)Catalyst4×HCID 10311-PropanolSolvent

Procedure

A warmed solution of 4-ethylidene-8-methoxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine, prepared as in example 3 (0.35 g, 1.83 mmol) in 30 mL of n-propanol is purged with a stream of nitrogen for 20 minutes prior to the addition of Wilkinson's catalyst, tris(triphenylphosphine)rhodium(I) chloride (0.025 g, 0.027 mmol). The reaction mixture is stirred at reflux for 15 hours under nitrogen and again treated with Wilkinson's catalyst (0.025 g). After 2 hr, the flask is charged with potassium carbonate (0.50 g, 3.60 mmol), and heated for 2 hr. The mixture is then treated with Wilkinson's catalyst (0.025 g). The mixture is heated to reflux for an additional 2 hr, filtered through Celite 545® and the filtrate is concentrated in vacuo. 1H NMR analysis shows a 1:8.3 ratio of exo- (4-ethylidene-8-methoxy-3,4-dihydro-1H-pyrano[3,4-c]pyridine) to endocyclic (4-ethyl-8-methoxy-1H-pyrano[3,4-c] pyridine) product. The dark residue is chromatographed on silica gel using 5% EtOAc/hexanes to provide 4-ethyl-8-methoxy-1H-pyrano[3,4-c]pyridine, the endocyclic form, as a colorless oil. 1H-NMR (CDCl3, 400 MHz): δ1.13 (t, J=7.4 Hz, 3H, --CH3); 2.30 (q, J=7.4 Hz, 2H, --CH2 --); 3.95 (s, 3H, --OCH3); 5.04 (s, 2H, --CH2O); 6.55 (d, J=5.4 Hz, 1H, Aromatic); 8.04 (d, J=5.4 Hz, Aromatic). Anal. Calcd for C11H13NO2.0.10CHCl3.0.05C3H8O: C, 65.54; H, 6.60; N,6.79. Found: C, 65.48; H, 6.57; N, 6.89. Mass Spectrum (FAB+): m/e 192 (M+1,100%).

Workup

  1. customis purged with a stream of nitrogen for 20 minutes
  2. temperatureat reflux for 15 hours under nitrogen
  3. temperatureheated for 2 hr
  4. temperatureThe mixture is heated
  5. temperatureto reflux for an additional 2 hr
  6. filtrationfiltered through Celite 545®
  7. concentrationthe filtrate is concentrated in vacuo
  8. customThe dark residue is chromatographed on silica gel using 5% EtOAc/hexanes

Sources & evidence

ORD record
ord-da56527865684d17a0fe4210eacf2170
Source dataset
uspto-grants-1996_02
Patent number
US05491237

Reaction notes

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