Dimethylformamide → HCID 15520892, compound

Participants

Reaction Steps

Sodium hydride (95%, 36.2 g, 1.51 mol) was placed into a dry 5 liter 3-necked round bottom flask under an atmosphere of argon. Anhydrous dimethylformamide (DMF) (2.0 liters) was added via canula followed by the careful addition of N-Boc-5-hydroxyanthranilic acid (150 g, 0.59 mol). The reaction mixture was cooled with an ice/water bath and benzyl bromide (148 mL, 1.24 mol) was added via syringe keeping the reaction temperature below 50° C. After addition was complete, the reaction mixture was stirred at 45° C.-50° C. for 6 hours. At this time additional benzyl bromide (35 mL, 0.29 mol) was added and the reaction continued at 45° C.-50° C. for an additional 2 hours. Acetic acid (20 mL) was carefully added and the reaction mixture was transferred to a round bottom flask and concentrated to a volume of approximately 400 mL. Ethyl acetate (1.0 liters) was added and the resulting solution was decanted from any solids present. The flask was rinsed with additional ethyl acetate (2×500 mL), decanting after each rinse. The combined organics were washed with water (1.0 liter) and saturated NaCl (500 mL). The organics were filtered and concentrated in vacuo to yield crude N-Boc-5-benzyloxyanthranilic acid, benzyl ester as a reddish brown syrup. The crude product was transferred to boiling hexanes (3 liters) and refluxed an additional 10 minutes. The solution was filtered while still hot and allowed to cool for 48 hours to yield 72 g of product (28% yield).

Provenance & Evidence