Dimethyl Sulfoxide → tert-Butyl 4-oxo-6-azaspiro[2.5]octane-6-carboxylate

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Reaction Steps

To a solution of oxalyl chloride (42.35 ml, 0.480 mol) in CH2Cl2 (910 ml) was added a solution of dimethylsulfoxide (68.24 ml, 0.961 mol) in CH2Cl2 (910 ml) at −70° C. within 45 min. The solution was stirred for 15 min and a solution of 4-hydroxy-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester (91.00 g, 0.400 mol) in CH2Cl2 (910 ml) was added within 40 min keeping the internal temperature at below −60° C. The mixture was stirred for 35 min and triethylamine (280.4 ml, 2.00 mol) was added at below −60° C. within 10 min. The cooling bath was removed and the yellow suspension was stirred for 1 h then quenched with water (1.4 l). The organic phase was separated, washed with water (3×1 l) and sat. aq. NaCl solution (3 l) and evaporated. The residual orange powder was dissolved in TBME (1.40 l), the turbid solution filtered (Hyflo Speedex) to remove some insoluble material and the clear filtrate evaporated to provide crude 4-oxo-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester as yellow powder (91.9 g). The material was re-dissolved in TBME (300 ml) and purified by filtration over silica gel (700 g) using a 3:1 heptane/TBME mixture (6.5 l). Evaporation and drying (10 mbar, 40° C.) afforded 4-oxo-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester as whitish powder (80.58 g, 89%), GC purity 100a %.

Provenance & Evidence