Chloroform → 1-[3-[5-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]phenyl]-3-phenyl-2(S)-propanol

Participants

Reaction Conditions

Reaction Steps

To a solution/suspension of 1-(3-bromophenyl)-3-phenyl-2(S)-propanol (260 mg, 0.89 mmol), 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5(trimethylstannyl)pyridine (417 mg, 0.98 mmol, 1.1 equiv.), Pd2dba3.CHCl3 (13.8 mg, 13.5 μmol, 15 mequiv.) and CsF (270 mg, 1.78 mmol, 2.0 equiv.) in N-methylpyrrolidone (1.0 mL) contained in a dried 100 mL round-bottom flask was added P(t-Bu)3 (10 wt % in hexane, 106 μL, 33 μmol) by syringe at room temperature under N2. The mixture was stirred for 3 h at 80° C., after which time TLC analysis indicated that the starting material had disappeared. After cooling, the reaction was quenched with saturated aqueous NH4Cl solution, and the mixture was extracted with EtOAc (3×50 mL). The organic layers were combined, dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was applied onto a silica gel column, which was eluted with CH2Cl2/MeOH 70:1 to give the product (280 mg, 66%) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 8.48 (br s, 1H), 8.35 (br s, 1H), 7.52-7.41 (m, 3H), 7.39-7.25 (m, 7H), 4.58 (m, 1H), 4.43 (m, 1H), 4.23 (dd, 1H, J=9.9, 3.0 Hz), 4.15 (m, 1H), 3.94 (t, 2H, J=7.2 Hz), 3.12-2.78 (m, 4H), 2.43-2.27 (m, 2H), 1.58 (OH and water), 1.43 (s, 9H). LC-MS (ESI) m/z 475 (M+H+).

Provenance & Evidence