1,8-Diazabicyclo(5.4.0)undec-7-ene → Methyl 6-methylisoquinoline-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a cold solution of 4-Dimethoxymethyl-pyridine-3-carbaldehyde (tetrahedron letters 2004 (45), 553-556) (400 mg, 1.91 mmol) in dichloromethane (10 ml) was slowly added a solution of Acetylamino-(dimethoxy-phosphoryl)-acetic acid methyl ester (synthesis 1984, 53-60) (503 mg, 2.1 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.31 ml, 2.1 mmol). The solution was stirred at 0° C. for 1 hour then at room temperature for 18 hours. The mixture was poured onto a cold saturated solution of sodium hydrogenocarbonate, extracted with dichloromethane, dried over sodium sulfate and concentrated to dryness. The residue was dissolved in toluene (49 ml) and treated with p-toleunesulfonic acid (315 mg, 1.66 mmol). The mixture was heated at reflux temperature for 18 hours and then concentrated under vacuum. The brown residue was dissolved in ethyl acetate, washed with a saturated solution of sodium hydrogenocarbonate, brine, dried over sodium sulfate and concentrated to yield methyl 6-methyl-isoquinoline-3-carboxylate (241 mg, 62%) as a brown solid.

Provenance & Evidence