Methyl iodide → 5-Methoxyanthranilic acid

Participants

Reaction Steps

To a stirred solution of NaH (washed three times with dry THF to remove oil, 0.145 g, 1.1 eq) in dry DMF (5 mL, CaH2 dried), 420 mg of methyl 3-hydroxy- 6-aminobenzoate (E) was added in 3 mL of DMF immediately followed by MeI (443 mg [0.195 m], 1.2 eq), and stirred at room temperature under argon for 16 hr, at which time TLC indicated the absence of E. 200 mL of CH2Cl2 was added and the mixture was extracted with brine (5×100 ml); the organic solvent was evaporated; the crude product was added to 200 mg of NaOH in 5 mL of water; and the reaction mixture was heated at 70° C. for 2 hr. The reaction mixture was neutralized to pH 7.0 with dilute HCl and extracted with CH2Cl2 (5×25 mL). The organic layer was dried over Na2SO4 and evaporated under reduced pressure to yield crude product, which was applied to silica gel (230-400 mesh and eluted with EtOAc/MeOH, 50:1) to yield product 39, 206 mg (yield 45%).

Provenance & Evidence