1-(((5S,7S)-3-(4-methoxybenzyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile → 1-(((5S,7S)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

Participants

Reaction Steps

A yellow solution of 1-(((5S,7S)-3-(4-methoxybenzyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (2.012 g, 4.53 mmol) in TFA (20.12 ml) was heated at 70° C. The reaction mixture turned dark brown overnight. Additional TFA (5 mL) was then added to the reaction mixture. After 21 h, additional TFA (5 mL) was added. After 23 h, reaction was completed as indicated by LCMS. The reaction mixture was then cooled to RT and concentrated. 2N NaOH (40 mL) and DCM (50 mL) were added to the mixture (aqueous layer was pH 13). The layers were separated and the aqueous layer was extracted with DCM (2×25 mL). Combined organic layers were dried over Na2SO4, filtered, and concentrated. The compound was loaded onto florisil and purified using silica gel chromatography CISCO): 1-5% MeOH/DCM (30 min), 5% (15 min), 40 g silica. Product began eluting at 22 minutes. The product was dried under high vacuum at 40° C. overnight to yield 1-{[(5S,7S)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile as a yellow solid (729 mg, 47.2% yield). MS (m/z) 325 (M+H+).

Provenance & Evidence