Acetic Acid → HCID 86751960, compound

Participants

Reaction Steps

n-Butyllithium (2.4M solution in hexane; 7.76 mL, 18.6 mmol) was added dropwise to a solution of 1-propanethiol (2.06 mL, 22.8 mmol) in THF (100 mL) at 0° C. After 1.5 h, a solution of (1R, 5S)-N-{(3R)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-[4-(2-(2-(trimethylsilyl)ethoxymethoxy)-1,1,1,3,3,3-hexafluoropropan-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 3 (9.43 g, 10.4 mmol) in THF (25 mL) was added dropwise, at 0° C., and the reaction mixture was stirred at room temperature for 3 h. The reaction was then quenched by the addition of 25% aqueous NH4OAc buffer. The aqueous layer was extracted with EtOAc (2×), and the combined organics were washed successively with 25% aqueous NH4OAc buffer and brine, dried (MgSO4) and concentrated. The residue was dissolved in EtOH (170 mL) and water (57 mL), lithium hydroxide monohydrate (2.20 g, 52.0 mmol) was added and the mixture heated to reflux for 2.5 h. The reaction mixture was cooled to room temperature before the addition of AcOH (3.56 mL, 62.1 mmol). After 30 min., 25% aqueous NH4OAc buffer was added and the aqueous layer extracted with EtOAc (2×). The combined organics were washed successively with 25% aqueous NH4OAc buffer and brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica (EtOAc/hexane 1:1) to afford the title compound as a colorless gum (4.08 g, 58%).

Provenance & Evidence