Sodium Bicarbonate → (+/-)-3-(5-Cyanobenzo[d]oxazol-2-yl)-3-(5-methoxy-7-methyl-1H-indol-4-yl)-2,2-dimethylpropanoic acid

Participants

Reaction Steps

A solution of (±)-tert-butyl 4-((5-cyanobenzo[d]oxazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 125-A) (133 mg, 0.31 mmol) in DCM (10 mL) was treated with TiCl4 (1M in DCM, 1 mL, 1 mmol) at 0° C. The reaction mixture was stirred for 15 min, followed by the addition of ((1-methoxy-2-methylprop-1-en-1-yl)oxy)trimethylsilane (0.36 g, 2 mmol). The mixture was allowed to reach room temperature over 1 h. The reaction mixture was then poured into aqueous NaHCO3. The organic layer was extracted with ethyl acetate (2×50 mL), and the combined organic layers were dried over Na2SO4, filtered and concentrated to provide a residue. The resulting residue was suspended in water (5 mL) and was treated wtih Dowex ion exchange resin (200% w/w) (washed with water twice). The reaction was stirred at 120° C. overnight in a sealed tube. Reaction was cooled, filtered and directly subjected to purification by FCC1-5% (MeOH:DCM) to obtain the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.05 (br. s., 1H) 7.46-7.61 (m, 1H) 7.23 (t, J=2.78 Hz, 1H) 7.10 (d, J=8.34 Hz, 2H) 6.69 (s, 1H) 6.31-6.51 (m, 1H) 4.19 (s, 1H) 3.72 (s, 3H) 2.45 (s, 3H) 1.60 (s, 3H) 0.93 (s, 3H). HMRS calcd. for C23H21N3O4 (M+H)+ 404.1602. found 404.1595.

Provenance & Evidence