Triethylamine → 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

Participants

Reaction Conditions

Reaction Steps

A 100-mL round-bottomed flask was charged with (2S)-2-((7-oxo-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylate and (2S)-2-((7-hydroxy-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-1,4-piperazinedicarboxylate (endo) (0.5 g) in EtOAc (20 mL) and 4N HCl in dioxane (0.85 mL, 3.4 mmol) was added. The reaction was heated to 70° C. for 2 h and after this time the precipitate was filtered, collected and dried. This material was dissolved in CH2Cl2 (10 mL). Triethylamine (0.75 mL, 5.4 mmol) followed by 5-nitrothiophene-2-sulfonyl chloride (0.26 g, 1.13 mmol, Enamine Building Blocks, Kiev, Ukraine) as a solution in CH2Cl2 (5 mL) were then added. After 10 min at room temperature, the reaction was concentrated onto silica and purified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (0.54 g).

Provenance & Evidence