Thionyl Chloride → cis-2-Methoxycarbonyl-3-methyltetrahydroquinoline

HRID 52516Notes

Reaction equation

HRID 52516 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[C@@H:14]([CH3:15])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6]1)=[O:4].C[O-].[Na+].S(Cl)(Cl)=O>CO>[CH3:1][O:2][C:3]([C@H:5]1[C@@H:14]([CH3:15])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6]1)=[O:4].[CH3:1][O:2][C:3]([C@H:5]1[C@H:14]([CH3:15])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6]1)=[O:4]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 10942334Sodium MethoxideHCID 67722227cis-2-Methoxycarbonyl-3-methyltetrahydroquinoline

Product 2

HCID 67721907trans-2-Methoxycarbonyl-3-methyltetrahydroquinolineYield 38%HCID 67722227cis-2-Methoxycarbonyl-3-methyltetrahydroquinolineYield 47%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of cis-2-methoxycarbonyl-3-methyltetrahydroquinoline (8.36 g, 40.7 mmol)in methanol (65 mL) was added sodium methoxide (14.8 mmol) in methanol (20 mL) at room temperature. The mixture was refluxed for 3 h and allowed to cool to room temperature. Thionyl chloride (7.23 mL, 99.2 mmol) was added and the resulting mixture was refluxed for 3 h. After the solvent was evaporated, the residue was dissolved in water and adjusted to pH 8 by using saturated aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate. The organic layer was washed with: water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by column chromatography with 15:1 hexane/ethyl acetate to give 3.94 g of cis-2-methoxycarbonyl-3-methyltetrahydroquinoline (47%) and 3.17 g of trans-2-methoxycarbonyl-3-methyltetrahydroquinoline (38%): 1H NMR (270 MHz, CDCl3) δ7.00 (td, 1H, J=7.3, 1 Hz), 6.93 (dd, 1H, J=7.3, 1Hz), 6.65 (td, 1H, J=7.3, 1 Hz), 6.58 (dd, 1H, J=7.3, 1 Hz), 4.22 (s, 1H), 3.74 (s, 3H), 3.70 (dd, 1H, J=5.9, 2.1 Hz), 2.79 (dd, 1H, J=15.8, 4.6 Hz), 2.44 (dd, 1H, J=15.8, 6.3 Hz), 2.35 (qddd, 1H, J =6.6, 6.3, 5.9, 4.6 Hz), 1.11 (d, 3H, J=6.6 Hz).

Workup

  1. temperatureThe mixture was refluxed for 3 h
  2. temperaturethe resulting mixture was refluxed for 3 h
  3. customAfter the solvent was evaporated
  4. dissolutionthe residue was dissolved in water
  5. extractionThe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with: water and brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography with 15:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-cdd2f99911a54e4bb31d8bd69727a0d7
Source dataset
uspto-grants-1997_04
Patent number
US05616586

Reaction notes

Loading…