(S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl ester → HCID 59371561, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3(R)-[(3-phenylpropoxy)methyl]pyrrolidine (220 mg, 1.00 mmol, 1.50 equiv.) and 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (240 mg, 0.67 mmol) in toluene (15 mL) were added sodium tert-butoxide (96 mg, 1.00 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (12 mg, 13.4 μmol, 0.02 equiv.) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 23 mg, 40 μmol, 0.06 equiv.) under N2. The mixture was stirred for 4 h at 100° C. After concentration in vacuo, the residue was diluted with water and extracted with EtOAc. The combined organic layers were dried and concentrated under reduced pressure. The residue was applied onto a silica gel column, which was eluted with EtOAc/petroleum ether 1:1 to afford the product (300 mg, 90%) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 7.68 (br s, 1H), 7.63 (br s, 1H), 7.37-7.19 (m, 5H), 6.43 (br s, 1H), 4.18-4.10 (m, 2H), 3.90 (br s, 1H), 3.49-3.29 (m, 9H), 3.13 (dd, 1H, J=9.0, 6.6 Hz), 2.74-2.61 (m, 3H), 2.20-2.12 (m, 1H), 2.06 (m, 2H), 1.99-1.82 (m, 5H). LC-MS (ESI) m/z 496 (M+H+).

Provenance & Evidence