Sodium bis(trimethylsilyl)amide → 8-(cyclopropylmethoxy)-4-hydroxy-7-methoxyquinolin-2(1H)-one

Participants

Reaction Steps

A solution of methyl 2-acetamido-3-(cyclopropylmethoxy)-4-methoxybenzoate (93%, 55 g, 175 mmol) and tetrahydrofuran (500 mL) was added dropwise (internal temperature kept below −65° C.) to a solution of sodium bis(trimethylsilyl)amide (NaHMDS) (691 mL, 1M toluene, 691 mmol) at −78° C. under N2. The cooling bath was removed, and the reaction was stirred overnight. The reaction was quenched with water/ice (1 L) and washed with diethyl ether (300 mL×2). The aqueous phase was adjusted to pH=3, with 6 N HCl. The resulting solids were collected by filtration, washed with water (500 mL×2), and dried in an oven to give 38.8 g of 8-(cyclopropylmethoxy)-4-hydroxy-7-methoxyquinolin-2(1H)-one as a yellow solid. MS (ESI): 262.0.

Provenance & Evidence