8-Methyl1,4-dioxaspiro[4.5]decane-8-carbonitrile synthesis

Yield:914780-97-5 84.84 %

Reaction Conditions:

Stage #1: 1,4-dioxaspiro[4.5]decane-8-carbonitrilewith bis(trifluoromethane)sulfonimide lithium in tetrahydrofuran at 0;
Stage #2: methyl iodide in tetrahydrofuran;

Steps:

92.1 1-Methyl-4-oxocyclohexane-1-carbonitrile (92b)

1,4-Dioxaspiro[4.5]decane-8-carbonitrile 92a (5.00 g, 29.9 mmol) was dissolved in THF (60 mL), and lithium bistrifluoromethanesulfonimide (9.87 mL, 34.38 mmol) was slowly added dropwise at 0 °C.
The reaction mixture was stirred for 1 h, and then iodomethane (4.24 g, 29.9 mmol) was slowly added.
The reaction mixture was stirred for another hour.
The reaction was monitored by TLC.
After completion of the reaction, the reaction mixture was extracted twice with saturated ammonium chloride solution, bromine water and ethyl acetate.
The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to get an intermediate 8-methyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile, which was then dissolved in THF (60 mL).
3 M HCl (60 mL) was added to the reaction mixture, which was then heated to 50 °C and stirred for 5 h.
The reaction was monitored by TLC.
After completion of the reaction, the reaction mixture was cooled to room temperature, the pH was adjusted to 7-8 with 3 M NaOH, and extracted 3 times with dichloromethane.
The organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the title compound 1-methyl-4-oxocyclohexane-1-carbonitrile 92b (yellow liquid, 3.48 g, 84.84% yield).
LC-MS m/z(ESI) = 138.10 [M+1]

References:

EP4137491,2023,A1 Location in patent:Paragraph 0845-0847