tert-butyl 4-oxo-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate synthesis

Yield:1346229-51-3 59.5%

Reaction Conditions:

Stage #1: 4-methylene-9-(t.butoxycarbonyl)-1-oxa-9-azaspiro[5.5]undecanewith water;osmium(VIII) oxide in 1,4-dioxane at 20; for 2 h;
Stage #2: with sodium periodate in 1,4-dioxane;

Steps:

29

4-Oxo-9-(t.butoxycarbonyl)-l-oxa-9-azaspiro[5.5]undecane (Compound 29b)To a solution of Compound 29a (1.6 g, 5.99 mmol) in a mixture of dioxane - water (32.9 ml and 1 1 ml respectively) under stirring at r.t.was added a 4% sol. of osmium tetroxide in water (0.762 μ, 0.125 mmol). After 2h, was added portionwise milled sodium metaperiodate (2.56 g, 12 mmol) affording a suspension that tended to become clear gray from brownish. After 4h H₂0 was added, extracting with EtOAc, washing with H₂0, drying over Na₂S0₄, evaporating the solvent to dryness. The residual tawny semi-solid was purified by automated flash chromatography (SP1TM - Biotage; Petroleum Ether - EtOAc 7 : 3) to give 0.96 g of the title compound as a grey solid. Yield: 59.5 %MS: [M+H]⁺ = 270.33

References:

WO2012/4400,2012,A1 Location in patent:Page/Page column 49