N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropyl]hydrazide

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Reaction Steps

To a stirring solution of 3.78 g (20 mmol) of N-[(1,1-dimethylethoxy)carbonyl]-β-alanine (6), prepared as described above in Example 6, and 5.79 (20 mmol) of 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)carboxylic acid, hydrazine (1), prepared as described above in Example 1, in 50 mL of DMF cooled in an icebath was added 3.5 mL (20 mmol) of DIEA followed by 4.22 g (22 mmol) of N,N-dimethylaminopropylethylcarbodiimide hydrochloride. The reaction was allowed to warm to ambient temperature over a period of 16 hours. To the reaction mixture was added 100 mL of EtOAc and 200 mL of M KHSO4. The layers were separated and then the organic layer was washed with 2×100 mL of M KHSO4, 2×100 mL of a saturated KHCO3 solution, and 100 mL of brine. The organic layer was dried over anhydrous Na2SO4, filtered, and then concentrated in vacuo. The resulting product was purified by column chromatography to yield 4.75 g (52%) of 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-oxopropyl]hydrazide (7). Analysis calculated for C22H25N4O5Cl.0.75 H2O (M.W. 474.43): C, 55.70; H, 5.63; N, 11.81. Found: C, 55.42; H, 5.76; N, 12.11.

Provenance & Evidence