Boron Trichloride → HCID 87058761, compound

Participants

Reaction Conditions

Reaction Steps

A 100-mL round-bottomed was charged with 6-(benzyloxy)-8-((2R)-2-piperazinylmethyl)-3-oxa-8-azabicyclo[3.2.1]octane tris-hydrochloride (0.400 g, 0.937 mmol, Example 79, Step 2), 10 mL of CH2Cl2, and thiazole-2-sulfonyl chloride (0.210 g, 1.031 mmol, Bioorg. Med. Chem., 2006, 14, 6628). The mixture was diluted with water and extracted with EtOAc. The combined organics were dried (MgSO4), filtered, and concentrated to give an oil. Purification via column chromatography on silica gel (0 to 10% MeOH in CH2Cl2, delivered the intermediate amine. To this was added 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.066 g, 0.23 mmol, Intermediate D), 2 mL of dioxane, and Hünig's base (0.049 mL, 0.281 mmol). The mixture was heated at 85° C. for 12 h then cooled to room temperature and purified by column chromatography on silica gel (0 to 50% EtOAc in hexanes) to give the intermediate benzyl protected alcohol. To this was added 4 mL of CH2Cl2 and BCl3 (1M in CH2Cl2, 0.937 mL, 0.937 mmol, Sigma-Aldrich, St. Louis, Mo.). After 30 min at room temperature, 5 mL of MeOH was added and the mixture was concentrated and purified by column chromatography on silica gel (0 to 10% MeOH in CH2Cl2) to give 8-(((S)-1-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)pyrimidin-2-yl)-4-(thiazol-2-ylsulfonyl)piperazin-2-yl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-ol (0.015 g) as a mixture of two isomers.

Provenance & Evidence