3-(4-Methoxy-benzyl)-3-aza-bicyclo[3.2.1]octan-8-one → 3-(4-Methoxy-benzyl)-8-(3-methoxy-phenyl)-3-aza-bicyclo[3.2.1]octan-8-ol

Participants

Reaction Conditions

Reaction Steps

3-(4-Methoxy-benzyl)-3-aza-bicyclo[3.2.1]octan-8-one (1.09 g, 4.44 mmol) was azeotroped from THF (3×50 mL) then dissolved in anhydrous THF (20 mL) under N2 and cooled to −78° C. This was treated with 3-methoxyphenylmagnesiumbromide (4.89 mL, 4.89 mmol) dropwise and stirred at −78° C. for 5 min, then warmed to room temperature. The reaction was quenched with 1N HCl (pH 1), washed with ether (2×50 mL), then the organic layer was back extracted with water (1×50 mL). The combined aqueous layers were neutralized to pH 8 with saturated aqueous NaHCO3 solution, extracted with CH2Cl2 (3×50 mL), washed with saturated aqueous NaCl solution (1×50 mL), dried through a cotton plug, and concentrated to yield a yellow oil (1.75 g, 100%). (TLC 50% EtOAc/hexanes Rf 0.30); 1H NMR (400 MHz, CDCl3) δ 7.26 (t, J=7.9 Hz; 2H), 7.05 (d, J=7.4 Hz, 1H), 7.01 (s, 1H), 6.84–6.78 (m, 4H), 3.77 (s, 3H), 3.76 (s, 3H), 3.52 (s, 2H), 2.83 (d, J=10.3 Hz, 2H), 2.58 (d, J=8.3 Hz, 2H), 2.36 (s, 2H), 1.75 (d, J=7.5 Hz, 2H), 1.41 (m, 2H); GCMS m/z 353 (M)+; APCI MS m/z 354.4 (M+1)+.

Provenance & Evidence