Water → tert-butyl 4-((1R,2R)-2-{[(5-bromopyridin-2-yl)methoxy]}cyclopropyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of tert-butyl 4-[(1R,2R)-2-(hydroxymethyl)cyclopropyl]piperidine-1-carboxylate (Intermediate 4: 3.5 g, 13.71 mmol) in THF (40 mL) was added NaHMDS (16.45 mL of a 1.0M soln in THF, 16.45 mmol) followed by the product of step A (4.13 g, 16.45 mmol) and the resulting mixture heated at reflux overnight. The mixture was cooled and poured into water (100 mL) and extracted with EtOAc (2×75 mL); combined EtOAc layers washed with sat. NaCl, dried over MgSO4, filtered and evaporated in vacuo. Residue purified by silica gel column chromatography (eluent: gradient 0-25% EtOAc in Hexanes) to give the title compound. 1H NMR (500 MHz, CDCl3) δ 8.82 (d, J 2.0 Hz, 1H), 7.84 (dd, J 8.0 & 2.0 Hz, 1H), 7.38 (d, J 8.0 Hz, 1H), 4.65 (d, J 13.5 Hz, 1H), 4.57 (d, J 13.5 Hz, 1H), 4.18-3.97 (br m, 2H), 3.64-3.58 (m, 1H), 3.58-3.52 (m, 1H), 2.74-2.58 (m, 2H), 1.86-1.79 (m, 1H), 1.77-1.69 (m, 1H), 1.47 (s, 9H), 1.36-1.20 (m, 3H), 0.98-0.89 (m, 1H), 0.79-0.68 (m, 2H), 0.07-0.03 (m, 1H).

Provenance & Evidence