Tetrabutylammonium Fluoride → HCID 86658430, compound

Participants

Reaction Steps

A solution of tert-butyl (2S,3S)-1-(N-(4-(tert-butyldimethylsilyloxy)phenyl)-trans-2-(pyridin-2-yl)cyclopropanecarboxamido)-3-methylpentan-2-ylcarbamate (720 mg, 1.3 mmol) and tetrahydrofuran (25 mL) was treated with tetrabutylammonium fluoride (1 M THF solution, 2.5 mL, 2.5 mmol). The reaction was maintained at room temperature for 2 h, then concentrated under reduced pressure to afford an oil that was purified by column chromatography on silica gel (eluting with 40% ethyl acetate in hexanes) to afford a mixture of diastereomers that was purified by chiral chromatography [Column: ChiralPak AD-H 4.6×250 mm, 25% solvent B (60% Ethanol in hexane) in solvent A (hexane) isocratic, retention time: 6.08 min.] to afford tert-butyl (2S,3S)-1-((1R,2R)—N-(4-hydroxyphenyl)-2-(pyridin-2-yl)cyclopropanecarboxamido)-3-methylpentan-2-ylcarbamate as an oil: 1H NMR (300 MHz, CDCl3) δ 8.96 (br. s., 1H), 8.12 (d, J=4.8 Hz, 1H), 7.39 (t, J=7.7 Hz, 1H), 7.09 (d, J=7.8 Hz, 1H), 6.79-6.95 (m, 3H), 6.54 (d, J=8.4 Hz, 2H), 5.13 (d, J=9.2 Hz, 1H), 4.28 (t, J=12.8 Hz, 1H), 3.49-3.66 (m, 1H), 2.87 (dd, J=13.6, 3.7 Hz, 1H), 2.47-2.61 (m, 1H), 1.84-1.98 (m, 1H), 1.38-1.47 (m, 1H), 1.32 (s, 9H), 1.23-1.28 (m, 1H), 0.85-1.01 (m, 1H), 0.73 (d, J=6.9 Hz, 3H), 0.68 (t, J=7.4 Hz, 3H); LRMS (ESI) m/e 454.2 [(M+H)+, calcd for C26H36N3O4 454.3].

Provenance & Evidence