An efficient synthesis of N-hydroxy-N'-[4-3H]phenyloctanediamide ([4-3H]SAHA), a potent cytodifferentiating agent

Article abstract of DOI:10.1002/(SICI)1099-1344(20000315)43:3<229::AID-JLCR307>3.0.CO;2-J

We have developed an efficient synthesis of N-hydroxy-N'-[4-³H]phenyloctanediamide ([4-³H]SAHA) from the monoester of suberanilic acid. The starting material, a monoester of suberoyl chloride, was condensed with 4-bromoaniline in the presence of a base to give the 4-bromoanilide of monoethyl suberate in 92% yield. On further treatment with methanolic hydroxylamine hydrochloride and sodium methoxide, this compound gave 4-bromosuberanilohydroxamic acid in 94% yield. Catalytic tritium exchange of bromine using Pd/C in a tritium gas atmosphere resulted in [4-³H]SAHA with a specific activity of 2.49 Ci/mmol. From the key intermediate, 4-bromoanilide of monoethyl suberate by a non-catalytic tritium exchange reaction, we have also prepared [4-³H]SAHA with high specific activity of 27.5 Ci/mmol.