Tetrahydrofuran → Methyl 3-(2-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoate

Participants

Reaction Conditions

Reaction Steps

To a sealed tube containing 72.2 (0.0980 g, 0.22 mmol), bis(dibenzylideneacetone)palladium (0.0068 g, 0.012 mmol), and CTC-Q-Phos (commercially available from Strem Chemicals.) (0.0083 g, 0.0116 mmol) was added dry THF (3.000 mL, 0.22 mmol). After about 5 minutes, 3-ethoxy-3-oxopropylzinc bromide, 0.5M solution in THF (1.000 mL, 0.50 mmol) was added dropwise. After 1 hour, the mixture was heated to 80° C. and monitored with TLC and LC-MS. After 16.5 hours, the reaction was cooled to room temperature and the organic solvent was then removed under reduced pressure. The residue was purified by flash chromatography (SiO2 gel 60, eluted with 0 to 40% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to a light brown oil (0.0646 g, 63%). 1H NMR (400 MHz) (CDCl3) δ ppm 8.11 (1H, d, J=5.3 Hz), 7.65 (1H, d, J=1.6 Hz), 7.32 (1H, dd, J=7.7, 1.7 Hz), 7.07 (2H, m), 6.85 (1H, dt, J=8.9, 3.6 Hz), 6.80 (2H, m), 6.70 (1H, s), 5.41 (2H, s), 4.15 (2H, q, J=7.2 Hz), 3.79 (3H, s), 2.93 (2H, t, J=7.6 Hz), 2.64 (2H, t, J=7.7 Hz), 1.29 (12H, m).

Provenance & Evidence