Hydrochloric Acid → Methyl 2-(6-methoxy-1H-inden-3-yl)butanoate

Participants

Reaction Conditions

Reaction Steps

An oven dried 5-L four-necked round-bottomed flask was fitted with a thermometer, a condenser, an addition funnel, and a mechanical stirrer. Under an argon atmosphere, a suspension of 5-methoxy-1-indanone (80.0 g, 494 mmol), Zn powder (Lancaster, 56.2 g, 865 mmol) in THF (2 L, anhydrous) was stirred at 60° C. (internal temperature), while a solution of methyl bromobutyrate (134.1 g, 741 mmol) in THF (400 mL, anhydrous) was added slowly using an addition funnel. After completion of the addition, the reaction mixture was stirred at 60° C. (internal temperature) for 1 h. The reaction was followed by TLC analysis of aliquots following 1 N aqueous HCl workup. After the reaction was completed, it was cooled in an ice-water bath followed by slow addition of HCl (3 L, 1 N aqueous solution). The internal temperature was kept below 20° C. The mixture was then extracted with EtOAc (1 L). The organic layer was washed with water until a pH of 6.0-7.0 was reached, then with brine, dried over Na2SO4, and then filtered. The product (127 g, >99%), a yellow oil, was obtained after solvent removal and drying under vacuum. 1H NMR (300 MHz), (DMSO-d6) δ 7.28 (d, 1H), 7.05 (d, 1H), 6.82 (dd, 1H), 6.22 (s, 1H), 3.72 (s, 3H), 3.60 (m, 1H), 3.58 (s, 3H), 3.28 (s, 2H), 1.95 (m, 1H), 1.80 (m, 1H), 0.88 (t, 3H).

Provenance & Evidence