1,2-Dichloroethane → HCID 90409507, compound

Participants

Reaction Steps

To a mixture of 2-(2-(1-(3-fluoro-5-(3-fluoro-4-methylphenoxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetic acid (23 mg, 0.053 mmol), HOBT (10 mg, 0.064 mmol), EDC (12 mg, 0.064 mmol) in THF (1 mL)/DMF (1 mL) was added 0-(tetrahydro-2H-pyran-2-yl)hydroxylamine (7.5 mg, 0.064 mmol) and TEA (0.074 mL, 0.53 mmol). The reaction mixture was stirred at rt overnight. After volatiles were removed in vacuo, the residue was dissolved in EtOAc (5 mL), then successively washed with 10% aq. citric acid (5 mL), sat′d aq. NaHCO3 (5 mL) and water (5 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude product (oil) was chromatographed [SiO2; gradient of EtOAc/hexanes (0% to 50% over 10 min)] to give the title compound (27 mg, 0.051 mmol, 96% yield) as a clear oil. [M+Na]+=554.4; 1H NMR (CDCl3) δ: 8.92 (s, 1H), 7.13 (t, J=8.7 Hz, 1H), 6.91-6.81 (m, 2H), 6.74-6.65 (m, 2H), 6.53 (dt, J=9.7, 2.3 Hz, 1H), 4.99 (t, J=3.0 Hz, 1H), 4.06-3.91 (m, 3H), 3.83 (s, 2H), 3.66 (dtd, J=11.3, 4.0, 1.7 Hz, 1H), 3.54 (t, J=6.9 Hz, 2H), 2.25 (d, J=2.0 Hz, 3H), 2.03-1.94 (m, 4H), 1.91-1.77 (m, 3H), 1.76-1.55 (m, 7H), 1.50 (t, J=6.8 Hz, 2H); 19F NMR (CDCl3) δ: −110.95, −114.13.

Provenance & Evidence