Methyl iodide → tert-butyl 1-acetyl-7-methyl-3-(methylsulfanyl)-4-oxo-6,7-dihydrothieno[3,4-c]pyridine-5(4H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

The tert-butyl 5-methyl-2,4-dioxopiperidine-1-carboxylate from Step 2 (3.65 g, 16.06 mmol) was dissolved in DMF (40.2 ml) and treated with cesium carbonate (15.70 g, 48.2 mmol). The mixture was evacuated under vacuum while stirring (10 min), then back-filled with nitrogen before being treated with the carbon disulfide (1.452 ml, 24.09 mmol) which caused an immediate color change from orange to red. This was stirred for 10 min, room temperature, before being cooled to 0° C. and treated with chloroacetone (1.279 ml, 16.06 mmol). This was stirred, 0° C., for 1 hr before being treated with iodomethane (1.105 ml, 17.67 mmol), allowed to warm to room temperature, and stirred for 18 hrs. The solvent was partially evaporated in vacuo, then the reaction mixture was diluted with CH2Cl2, washed with sat'd brine (×4), dried (Na2SO4), filtered and evaporated to give a dark red oil. This was chromatographed (SiO2, 0-30% EtOAc/hexanes) to give the title compound. 1H NMR (400 MHz, CDCl3) 4.22 (dd, J=13.2, 1.8 Hz, 1H), 3.76 (m, 1H), 3.60 (dd, J=13.2, 3.4 Hz, 1H), 2.63 (s, 3H), 2.50 (s, 3H), 1.57 (s, 9H), 1.30 (d, J=7.1 Hz, 3H).

Provenance & Evidence