Hydrochloric Acid → HCID 53823624, compound

Participants

Reaction Steps

n-Butyllithium (2.4M solution in hexane; 10.6 mL, 25 mmol) was added dropwise to a 0° C. solution of propanethiol (4.6 mL, 51 mmol) in THF (150 mL). After 15 minutes, (1R, 5S)-N-{(3R)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-[4-(1,3-dioxolan-2-yl)phenyl]-2-(4-pyridyl)propanoyl}-10,10-dimethyl-3-thia-4-azatricyclo[5.2.1.01,5 ]decane-3,3-dioxide from Step 2 (9.7 g, 14.1 mmol) was added as a solid and the reaction mixture was stirred at room temperature for 3 days. The volatiles were then evaporated and the resulting residue was dissolved in EtOH (80 mL) and water (40 mL). Sodium hydroxide (4.5 g, 113 mmol) was added and the mixture heated to reflux for 2 hours. The reaction mixture was cooled to room temperature and treated with HCl 6N to pH 4.5 then heated to reflux for 1 hour. The reaction mixture was cooled to room temperature and treated with NaOH 1N to pH 14 then extracted twice with EtOAc. The organic phase was washed with brine, dried (MgSO4) and evaporated. The residue was purified by flash-chromatography (silica gel, ether) to afford the title compound as a white foam (2.3 g, 41%). 1H NMR (400 MHz, CDCl3): δ 1.55 (m, 2H), 1.75 (m, 6H), 3.30 (m, 2H), 3.80 (s, 3H), 4.20 (t, 1H), 4.60 (m, 1H), 6.60 (s, 1H), 6.65 (d, 1H), 6.75 (d, 1H), 6.90 (d, 2H), 7.35 (d, 2H), 7.75 (d, 2H), 8.40 (d, 2H), 9.95 (s, 1H).

Provenance & Evidence