1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 3-[4-[2-[4-(Benzyloxy)phenoxy]ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine

Participants

Reaction Conditions

Reaction Steps

A solution/suspension of 4-[2-[4-(benzyloxy)phenoxy]ethyl]piperidine (220 mg, 0.71 mmol), 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (277 mg, 0.78 mmol, 1.1 equiv.), sodium tert-butoxide (136 mg, 1.42 mmol, 2.0 equiv.), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (45 mg, 40 μmol, 0.06 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 50 mg, 90 μmol, 0.12 equiv.) in anhydrous toluene (20 mL) was stirred overnight at 100° C. under N2. After cooling to room temperature, the mixture was concentrated under vacuum, and the residue was taken up in 500 mL of EtOAc and washed with brine. The organic layer was dried and concentrated in vacuo, and the residue was applied onto a silica gel column, which was eluted with EtOAc/CH2Cl2 1:5 to 1:2 to provide the title compound (300 mg, 72%) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 7.90 (s, 1H), 7.67 (s, 1H), 7.46-7.34 (m, 5H), 7.08 (s, 1H), 6.93 (d, 2H, J=9.3 Hz), 6.85 (d, 2H, J=9.3 Hz), 5.02 (s, 2H), 4.18-4.13 (m, 3H), 4.00 (t, 2H, J=5.7 Hz), 3.76 (m, 2H), 3.41 (m, 2H), 2.83 (s, 2H), 2.07-2.03 (m, 2H), 1.90-1.72 (m, 3H), 1.77 (m, 3H), 1.49 (s, 9H), 1.40-1.30 (m, 2H), 1.28-1.26 (m, 1H). LC-MS (ESI) m/z 588 (M+H+).

Provenance & Evidence