Methanol → 5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzonitrile

Participants

Reaction Steps

A flask was charged with methyl 2-(5-(2-cyano-4-fluorophenoxy)-1H-indazol-1-yl)acetate (100.0 g, 307.4 mmol) and MeOH (620 mL, 0.5M) and purged with nitrogen, Sodium borohydride (40.00 g, 1057 mmol) was added portionwise to the reaction mixture over 2.5 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. To the residue were added 1000 mL of saturated aqueous NH4Cl solution and 1000 mL of EtOAc. The mixture was stirred for 1 hour at ambient temperature. The layers were separated and the aqueous layer was extracted with EtOAc. The combined extracts were washed with saturated NH4Cl and brine, dried over MgSO4, filtered through a Celite pad, and concentrated under reduced pressure to provide 91.1 g of the crude product. The crude solid was dissolved in CH2Cl2 (1500 mL). Hexanes (2500 mL) were added to the solution with stirring. The light brown solid which crashed out of solution was filtered, washed with 1:2 CH2Cl2:hexanes and dried under high vacuum to provide 84.8 g (92.8%) of the title product. 1H NMR (400 MHz, CdCl3) δ 7.98 (s, 1H), 7.50 (d, J=8.98 Hz, 1H), 7.39-7.35 (m, 2H), 7.21-7.15 (m, 2H), 6.80 (dd, J=4.29 Hz. 9.37 Hz, 1H), 4.49 (t, J=5.00 Hz, 2H), 4.19-4.10 (m, 2H), 2.90 (br s, 1H).

Provenance & Evidence