Boron Trichloride → 8-(((2S)-4-(2-thiophenylsulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-ol

Participants

Reaction Conditions

Reaction Steps

A 25-mL round-bottomed flask was cooled to 0° C. and charged with 2-(2-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (endo) (170 mg, 0.26 mmol) and CH2Cl2 (5 mL). BCl3 (1M in CH2Cl2, 4.20 mL, 4.20 mmol) was added slowly. After 15 min at 0° C., the reaction was carefully quenched with MeOH and concentrated. The resultant foam was then recrystallized from MeOH/ether to yield an off-white solid which was purified via column chromatography (12 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 8-(((2S)-4-(2-thiophenylsulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-ol (120 mg) (endo) as a mixture of four isomers.

Provenance & Evidence