Phosphorus oxychloride → 1-Methyl-5,6,7-trimethoxy-3,4-dihydroisoquinoline
Reaction equation
[CH3:1][O:2][C:3]1[C:14]([O:15][CH3:16])=[C:13]([O:17][CH3:18])[CH:12]=[CH:11][C:4]=1[CH2:5][CH2:6][NH:7][C:8](=O)[CH3:9].O=P(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[CH3:9][C:8]1[C:11]2[C:4](=[C:3]([O:2][CH3:1])[C:14]([O:15][CH3:16])=[C:13]([O:17][CH3:18])[CH:12]=2)[CH2:5][CH2:6][N:7]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of the acetamide 43 (280 mg, 1.1 mmol) in toluene (5 mL) containing POCl3 (0.8 mL, 8.5 mmol) was heated at reflux under Ar for 2 h. The excess POCl3 and the solvent were evaporated under vacuum. The black residue was washed with petroleum ether (10 mL). The residue was dissolved in distilled water (10 mL) and made basic by 5% NH4OH aq (10 mL). The aqueous solution was extracted with CHCl3 (20, 10, and 5 mL). The combined CHCl3 layer was washed successively with water (10 mL) and saturated NaCl solution (10 mL) and dried over anhydrous Na2SO4. Evaporation of the filtrate and chromatography (ether:ethanol, 98:2 by volume, silica gel 230-400 mesh) gave compound 44 as a pale brown oil (230 mg, 89.2%): 1H NMR (CDCl3, 200 MHz) δ6.84 (s, 1H), 3.92 (s, 3H), 3.89 (s, 3H), 3.85 (s, 3H), 3.61 (t, 2H, J=8 Hz), 2.64 (t, 2H, J=8 Hz), 2.36 (s, 3H). EIMS m/e 235 (M+, 84).