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

Temperature

0 °C

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.

1. waitat room temperature for 18 hours
2. extractionextracted with dichloromethane
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated to dryness
5. dissolutionThe residue was dissolved in toluene (49 ml)
6. temperatureThe mixture was heated
7. temperatureat reflux temperature for 18 hours
8. concentrationconcentrated under vacuum
9. dissolutionThe brown residue was dissolved in ethyl acetate
10. washwashed with a saturated solution of sodium hydrogenocarbonate, brine
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated

ORD record

ord-9472ff5011434884ad2bdd85d6a2b29c

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962627B2