Formaldehyde → 2,7-Diazaspiro[3.5]nonane-2-carboxylic acid, 7-methyl-, 1,1-dimethylethyl ester

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Reaction Steps

To a solution of 2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester hydrochloride (100 mg, 0.381 mmol) in DCE (10 mL) was added an aqueous solution of formaldehyde (37% w/w, 40 μL, 0.537 mmol). The mixture was stirred at RT for 10 min, then sodium triacetoxyborohydride (121 mg, 0.571 mmol) was added and stirring was continued for 1 h. Water was added to the reaction mixture before being loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH then eluted with 2 M NH3 in MeOH to give 7-methyl-2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester. To a solution of 7-methyl-2,7-diaza-spiro[3.5]nonane-2-carboxylic acid tert-butyl ester in DCM (5 mL) was added TFA (1 mL) and the resulting mixture was stirred at RT for 1 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give the title compound as a colourless oil (45 mg, 84%).

Provenance & Evidence