Boron trifluoride → 2-Methyl-3-{5-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-thiophen-2-yl}-2-phenoxy-propionic Acid Methyl Ester

Participants

Reaction Conditions

Reaction Steps

To a solution of triethylsilane (0.62 mL, 3.89 mmol) in CH2Cl2 (4 mL) at −20° C., boron trifluoride diethyl etherate (0.49 mL, 3.89 mmol) was added. A solution of 3-{5-[1-hydroxy-3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-thiophen-2-yl}-2-methyl-2-phenoxy-propionic acid methyl ester (650 mg, 1.30 mmol) in CH2Cl2 (4 mL) was then added dropwise to the BF3 solution over 1 h, keeping the temperature at −15° C. The reaction was stirred at 0° C. for 2 h. The reaction was quenched with 1 N NaOH (approx. 3.6 mL) diluted with 1.8 mL of water and the pH was adjusted to pH 4.0 using 1 N HCl and 1 N NaOH. The organic layer was separated and the aqueous layer was further extracted with CH2Cl2 (2×30 mL). The combined organic layers were then washed with 0.1 N HCl (30 mL) and water (2×30 mL). Xylene (15 mL) and NaCl were added and the organics were concentrated to dryness to yield a yellow oil. The product was used in the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 7.95 (d, 2H), 7.37 (m, 4H), 7.20 (m, 1H), 6.96 (t, 1H), 6.84 (d, 2H), 6.60 (dd, 2H), 3.72 (s, 3H), 3.41 (d, 1H), 3.30 (d, 1H), 2.78 (t, 2H), 2.50 (t, 2H), 2.24 (s, 3H), 2.00 (m, 2H), 1.43 (s, 3H); MS (EI) 476.2 (M+H)+.

Provenance & Evidence