The title compound was synthesized by two procedures. Indomethacin (I) was coupled with 3-hydroxybenzyl nitrate (II) using DCC to yield the title ester.

Alternatively, coupling of 3-hydroxybenzaldehyde (I) with acetylsalicyloyl chloride (II) by means of Et3N in dichloromethane affords 2-acetoxybenzoic acid 3-formyl-phenyl ester (IV), which is then reduced by hydrogenation over Pd/C in ethyl acetate to provide alcohol (III). Chlorination of alcohol (III) by treatment with thionyl chloride in DMF gives the chloromethyl derivative (V), which is finally converted to NCX-4016 by treatment with AgNO3 in refluxing acetonitrile.

In a related procedure, indomethacin chloride (III) was coupled with 3-hydroxybenzaldehyde (IV) to yield ester (V). Catalytic hydrogenation of the formyl group of (V) over Pd/C produced alcohol (VI), which was further converted to chloride (VII) upon treatment with SOCl2. The chloride group of (VII) was finally displaced with silver nitrate to furnish the corresponding nitrate ester.