Triethylamine → 9-(((2S)-4-((6-chloro-3-pyridinyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol

Participants

Reaction Steps

A 25-mL round-bottomed flask was charged with a 1:1 mixture of 9-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2R)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (215 mg, 0.44 mmol), triethylamine (0.19 mL, 1.33 mmol) and CH2Cl2 (5 mL). 6-chloropyridine-3-sulfonyl chloride (94 mg, 0.44 mmol, Organic Process Research & Development 2009, 13, 875) was added as a solution in CH2Cl2 (2 mL) and the reaction was stirred at room temperature for 20 min. The reaction was then concentrated onto silica and purified via column chromatography (12 g silica gel, 0 to 100% EtOAc in hexanes) to give 9-(((2S)-4-((6-chloro-3-pyridinyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) and 9-(((2S)-4-((6-chloro-3-pyridinyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (50 mg).

Provenance & Evidence