Water → HCID 86684919, compound

Participants

Reaction Steps

To a stirred suspension of 4-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-benzenethiol (30.4 g, 110 mmol) and benzenesulfonate (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-methyl-cyclopropanecarbonyl)-pyrrolidin-3-yl ester (41.7 g, 100 mmol) in THF (50 mL) was added at room temperature 20% lithium tert-butoxide in THF (44.0 g≅49.5 mL, 110 mmol) over 40 min. After stirring at room temperature for 18 h, the reaction mixture was hydrolyzed with deionized water (400 mL) and extracted twice with ethyl acetate (400 mL & 200 mL). Both organic layers were washed with 10% brine (200 mL), combined, dried over Na2SO4, and filtered. Evaporation of the solvent and careful drying (45° C./≧10 mbar) gave 56.3 g crude product as voluminous, off-white foam, which was dissolved in 250 mL toluene at 50° C. The crystallization, which started during cooling, was completed after stirring at room temperature for 1 h by the dropwise addition of 200 mL heptane (note 11), followed by stirring at room temperature for 20 h. Filtration and drying (50° C./10 mbar/3 days for removal of toluene to ˜1%) yielded 51.2 g (95.7%) title product as an off-white crystalline powder, mp. 66-76° C. [α]D20=−67.5 (c 1.0; CHCl3). 1H NMR (CDCl3, 400 MHz) δ0.55-0.70 (m, 2H), 0.87-0.95 (m, 1H), 1.02-1.10 (m, 1H), 1.13-1.23 (m, 2H), 1.31 (s, 3H), 1.42-1.55 (m, 2H), 1.85-1.97 (m, 1H), 2.74-2.85 (m, 1H), 3.80-4.00 (m, 3H), 4.40 (q, J=7.8 Hz, 2H), 4.60 (dd, J1=8.1 Hz, J2=4.6 Hz, 1H), 7.11 (dd, J1=8.6 Hz, J2=2.7 Hz, 1H), 7.30 (d, J=3.0 Hz, 1H), 7.61 (d, J=8.6 Hz, 1H), 8.05 (s, 1H).

Provenance & Evidence