Potassium Hydroxide → 2-(6-methoxy-1H-inden-3-yl)butanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of the ester prepared in Example 16 (200.0 g, 813 mmol) in MeOH (2 L), was added a solution of KOH (91.0 g, 1.63 mol) in water (200 mL). The reaction mixture was stirred at 60° C. (internal temperature) for 2 h. TLC showed 70% conversion. A solution of KOH (45.0 g, 0.81 mol) in water (100 mL) was then slowly added to the reaction mixture. The reaction was complete in 1 h, after which the mixture was cooled to rt, and then the solvents were removed at under reduced pressure. The residue was dissolved in water (3 L), and then washed with EtOAc (2×1 L). The aqueous layer was cooled in an ice-water bath, acidified with HCl (37% aqueous solution) to pH<3.0 and extracted with CH2Cl2 (3 L). The organic phase was washed with water (2×1 L), dried over Na2SO4, filtered, and then the filtrate was stirred with 30.0 g charcoal for 2 h. The charcoal was removed by filtration through a pad of Celite® to provide the title compound (175 g, 93%) as a light brown solid after solvent removal and drying under reduced pressure. 1H NMR (300 MHz), (DMSO-d6) δ 12.20 (b, 1H), 7.30 (d, 1H), 7.06 (d, 1H), 6.82 (dd, 1H), 6.22 (s, 1H), 3.75 (s, 3H), 3.45 (t, 1H), 3.30 (s, 2H), 1.90 (m, 1H), 1.78 (m, 1H), 0.90 (t, 3H).

Provenance & Evidence