Sodium hydride → 5-Oxo-4-(3-piperidin-1-yl-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester

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Reaction Steps

A solution of 8.52 g (39.75 mmol) of 5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester in 200 ml of DMA was treated at 0° C. with 2.60 g (59.62 mmol) of NaH (55% dispersion in oil) in small portions. The reaction was stirred 1 h at this temperature, then the free 1-(3-chloropropyl)piperidine in 200 ml toluene was dropped in [49.62 g (250.42 mmol, 6.3 eq.) 1-(3-chloropropyl)piperidine hydrochloride were dissolved in 262 ml of 1 M aq. 1N NaOH solution and extracted with toluene (200 ml). The organic phase was dried over Na2SO4]. The reaction was warmed up to RT and stirred over night. After 2 h at 50° C. and cooling to RT, the reaction was neutralized with water (50 ml), evaporated and then dissolved in aq. sat. NaHCO3 solution/Et2O. After reextraction with Et2O, the organic phase was dried (Na2SO4), evaporated and crystallized from pentane to yield 12.08 g (90%) of the title compound as white crystals. MS: 340.2 (MH+).

Provenance & Evidence