Hydrochloric Acid → HCID 57252838, compound

Participants

Reaction Steps

n-Butyllithium (2.4M solution in hexane; 13.2 mL, 31.3 mmol) was added dropwise to a solution of 1-propanethiol (3.47 mL, 38.3 mmol) in THF (160 mL) at 0° C. After 30 min, (1R,5S)-N-{(3R)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-[4-(1,3-dioxolan-2-ylmethyl)phenyl]-2-(4-pyridyl)propanoyl}-10,10-dimethyl-3-thia-4-azatricyclo[5.2.1.01,5 ]decane-3,3-dioxide from Step 3 (12.2 g, 17.4 mmol) was added as a solid and the reaction mixture was stirred at room temperature for 2.5 h. The volatiles were then evaporated and the resulting residue was dissolved in EtOH (100 mL) and water (50 mL). Sodium hydroxide (5.57 g, 139 mmol) was added and the mixture heated to reflux for 2.5 h. The reaction mixture was cooled to room temperature and treated with 6N HCl to pH 4.5 then heated to reflux for 2 h. The reaction mixture was cooled to room temperature and treated with 1N NaOH to pH 14, then extracted with EtOAc (3×). The combined organics were washed successively with 25% aqueous NH4OAc buffer, water and brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica (acetone/ether 1:9→1:4→1:3) to afford the title compound as an off-white gum (1.17 g, 14%).

Provenance & Evidence