Sodium t-butoxide → HCID 86684920, compound

Participants

Reaction Steps

3-[4-(2-Methyl-pyridin-4-yl)-2-trifluoromethyl-phenylsulfanyl]-propionamide (200 g, 588 mmol) was dissolved in tetrahydrofuran (1.0 L) before sodium tert-butoxide (55.5 g, 578 mmol) was added and the fine suspension was stirred for 2 h at room temperature. N,N-dimethylacetamide (500 mL) was added and the solution was stirred for further 1.5 h. A solution of benzenesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidin-3-yl ester (237.5 g, 504 mmol) in N,N-dimethylacetamide (500 mL) was added and the brown, clear solution was stirred for 40 h. The mixture was diluted with water (3 L) and extracted with tert-butyl methyl ether (1×2 L, 3×1 L). The combined organic extracts were washed with an aqueous sodium carbonate solution (1 M, 1.0 L) and brine (1.0 L), dried over sodium sulfate, and concentrated in vacuo to yield the title compound as a brown gum (327.8 g). The crude product (containing dimethylacetamide) was used in the next step without further purification. For characterization purposes, a 4 g sample of crude material was purified by filtration over silica gel (20 g, eluent: ethyl acetate (200 mL)). 3.3 g of purified material were obtained as an off-white solid. MS (EI): m/z=583.1 [M+H]+. 1H NMR (CDCl3, 300 MHz): δ 1.10-1.36 (m, 6H), 1.49-1.58 (m, 2H), 1.99-2.12 (m, 1H), 2.65 (s, 3H), 2.90-3.02 (m, 1H), 3.92 & 4.02 (ABX, JAB=11.9 Hz, JAX=4.8 Hz, JBX=5.8 Hz, each 1H), 4.12-4.22 (m, 1H), 4.71 (dd, J=4.7 Hz, 7.8 Hz, 1H), 7.31 (d, J=5.3 Hz, 1H), 7.37 (br s, 1H), 7.60-7.69 (m, 2H), 7.80 (d, J=8.3 Hz, 1H), 7.93 (s, 1H), 8.60 (d, J=5.1 Hz, 1H).

Provenance & Evidence