Ethyl chloroacetate → 6-Methyl-5-nitroisoquinoline

Participants

Reaction Steps

To a suspension of potassium tert-butoxide (4.25 g, 37.9 mmol) in 13 mL of THF at −10° C. under an atmosphere of nitrogen was added a solution of 5-nitroisoquinoline (3.00 g, 17.2 mmol) and ethyl chloroacetate (2.32 g, 18.9 mmol) in 18 mL of THF dropwise. After 3 h, water (30 mL) was added and the reaction was stirred at rt for 3 d. Potassium carbonate (5.95 g, 43.1 mmol) was added, and after 24 h, the mixture was heated to 40° C. After 24 h, additional potassium carbonate (1.19 g, 8.62 mmol) was added, and the reaction was heated to 50° C. for another 3 h, then cooled to rt. The mixture was concentrated in vacuo, azeotroped 3× with toluene, and redissolved in dichloromethane. The organic solution was washed 3× with water, then with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to provide 6-methyl-5-nitroisoquinoline that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 189.2 for [M+H]+.

Provenance & Evidence