Methanol → HCID 83675281, compound

Participants

Reaction Conditions

Reaction Steps

Compound 429 (631 mg, 2.57 mmol) was dissolved in THF (20 mL) and stirred at 0° C. under Argon. 2 M LAH in THF (3 eq, 15 mL) was added dropwise. The resulting mixture was warmed to rt for 1 h and volatiles were evaporated in vacuo. The residue was carefully quenched with ice-cold 0.5 N HCl (200 mL) and then extracted with EtOAc (200 mL). The organic layer was separated and dried over Na2SO4. The resulting crude oil was purified by chromatography (30% to 70% EtOAc/hexanes) to provide a crude yellow solid, which demonstrated ˜85% purity based on 1H NMR. The impurity was determined to be a partially reduced alkene intermediate. The yellow solid was further reacted by dissolving in EtOAc (10 mL) and MeOH (10 mL) in a glass hydrogenation flask. 10% Pd/C (58 mg, 10% w/w) was added and the sample was hydrogenated for 4 h at 35 psi of H2 to ensure complete reduction. The mixture was filtered over Celite and purified by chromatography (20% to 70% EtOAc/hexanes) to yield a light-yellow solid (216 mg, 41%): mp 85-88° C. (lit.19 62-65° C.). TLC Rf 0.22 (50% EtOAc/hexanes). 1H NMR (600 MHz, CDCl3) δ 8.07 (s, 1H), 7.18-7.17 (d, 1H, J=8.7 Hz), 7.01 (d, 1H, J=2.4 Hz), 6.78-6.77 (dd, 1H, J1=8.7 Hz, J2=2.46 Hz), 6.19-6.18 (d, 1H, J=1.98 Hz), 3.84 (s, 3H), 3.75-3.73 (t, 2H, J=6.06 Hz), 2.87-2.85 (t, 2H, J=7.2 Hz), 1.97-1.94 (quin, 2H, J=6.12 Hz). 13C NMR (150 MHz, CDCl3) δ 154.2, 140.0, 131.2, 129.3, 111.16, 111.04, 102.1, 99.7, 62.3, 56.0, 31.9, 24.9. Elemental analysis for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.10; H, 7.23; N, 6.74.

Provenance & Evidence