Benzylamine → Tert-butyl 9-benzyl-7-oxo-3,9-diazabicyclo[3.3.1]nonane-3-carboxylate

Participants

Reaction Steps

Acetone-1,3-dicarboxylic acid (13.8 g, 94.96 mmol) and sodium acetate (7.94 g, 96.8 mmol) were added to a solution of bis-(2-oxo-ethyl)-carbamic acid tert-butyl ester (19.1 g, 94.96 mmol) in H2O (118 mL). Benzylamine (10.3 mL, 94.96 mmol) was dissolved in aqueous HCl (3 N, 63 mL) and was subsequently added to the stirring solution of the dialdehyde and the dicarboxylic acid over a 15 minute period. The reaction mixture was stirred for 3 days at room temperature after which the pH was adjusted to 8 by the addition of potassium carbonate. The resulting solution was extracted with methylene chloride (4×70 mL), the organic extracts dried (Na2SO4), filtered and concentrated under vacuum. The resulting residue was purified by silica gel chromatography, (eluant hexane/EtOAc 9/1 to 1/1, v/v), to give 15.1 g (48%) of 9-benzyl-7-oxo-3,9-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester as a brown oil. Retention time (min)=1.195, method [1], MS(ESI) 331.2 (M+H); 1H NMR (300 MHz, CDCl3) δ 7.43-7.15 (m, 5H), 4.00-3.81 (m, 4H), 3.21 (bs, 2H), 3.20-2.98 (m, 2H), 2.62 (dd, J=15.9 Hz, 5.5 Hz, 2H), 2.28-2.17 (m, 2H), 1.42 (s, 9H).

Provenance & Evidence