1,8-Diazaspiro[4.5]decane, 8-Methyl- synthesis

Yield:-

Reaction Conditions:

Stage #1: tert-butyl 1,8-diazaspiro[4.5]decane-1-carboxylate hydrochloridewith sodium hydroxide in methanol;water;
Stage #2: formaldehydwith sodium cyanoborohydride in methanol;water at 20; for 4 h;

Steps:

60

tert-Butyl 1,8-diazaspiro[4.5]decane-1-carboxylate, HCl (150 mg, 0.542 mmol) was dissolved into MeOH (2.5 mL), neutralized with 1M NaOH aq. (0.50 mL) and treated with formalin (1.3 mL) and then sodium cyanoborohydride (51 mg, 0.81 mmol). The reaction was stirred at rt for 4 h, partitioned between EtOAc and water and the organic layer was concentrated to dryness. The residue was dissolved into DCE (1 mL) and TFA (1 mL) was then added. The reaction was stirred 3 h and concentrated to dryness under vacuum to yield-methyl-1,8-diazaspiro[4.5]decane as a yellow oil which was used without further purification.

References:

US2009/130056,2009,A1 Location in patent:Page/Page column 48