Ethyl 3-methyl-4-oxo-cyclohexanecarboxylate synthesis

Yield:1207529-72-3 37%

Reaction Conditions:

Stage #1: ethyl 4-oxocyclohexane-1-carboxylatewith lithium hexamethyldisilazane in tetrahydrofuran at -78; for 1 h;Inert atmosphere;
Stage #2: methyl iodide in tetrahydrofuran at 20; for 2 h;

Steps:

12A.1 Step 1: Preparation of ethyl 3-methyl-4-oxocyclohexanecarboxylate (M-1).

Step 1: Preparation of ethyl 3-methyl-4-oxocyclohexanecarboxylate (M-1).To a solution of ethyl 4-oxocyclohexanecarboxylate (10 g, 58 mmol) in THF (100 mL) was added LiHMDS (65 mL, 65 mmol) portionwise, while stirring at -78 °C under N2. After stirring for 1 h, iodomethane (8.34 g, 58 mmol) was added dropwise. The mixture was stirred at ambient temperature for 2 h. The mixture was diluted with water (150 mL) and extractedwith EtOAc (100 mLx3). The combined organics were washed with brine, dried overNa2SO4 and evaporated. The residue was purified by silica gel chromatography, eluting withPE:EA = 30:1 to afford the title compound (4 g, yield: 3 7%). LCMS (ESI) calc’d forC,0H,603 [M+H]: 185, found: 185.

References:

WO2014/28597,2014,A2 Location in patent:Page/Page column 90