Water → 3-Phenyl-5,6,8,9-tetrahydroimidazo[1,5-d][1,4]-oxazepine-1-carboxylic acid

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Reaction Conditions

Reaction Steps

(E)-5-methoxy-2,3,6,7-tetrahydro-1,4-oxazepine (50 mg, 0.387 mmol) was dissolved in THF (1 mL) in a screw-cap vial and 2-phenyloxazol-5(4H)-one (62.4 mg, 0.387 mmol) was added to give a orange solution. The reaction was heated to 150° C. for 5 minutes. LCMS shows two peaks of the corresponding product mass (tautomers of the condensation), Rt 0.73 and 0.78 minutes. The reaction was concentrated under reduced pressure and the residue was dissolved in 1 mL MeOH and treated with lithium hydroxide monohydrate (81 mg, 1.936 mmol) and water (200 μL). The reaction was heated at 120° C. for 5 minutes using microwave irradiation to provide a new desired product (same MW as intermediate) with Rt=0.50 minutes. The reaction was concentrated to remove MeOH and then diluted with water (1 mL). The solution was acidified to pH2 with 5N HCl. The solution was extracted with DCM (3×2 mL). The combined organic extracts were dried and evaporated to provide the title compound as a brown oil (23 mg). Additional material was recovered by concentrating the aqueous layer and repeated extraction with DCM. The combined material (45 mg, 45%) was used without further purification. LCMS (+ESI) m/z: 130.2 [M+H]+

Provenance & Evidence