tert-Butyl piperazine-1-carboxylate → HCID 69418500, compound

Participants

Reaction Conditions

Reaction Steps

A third intermediate compound, 1-(8-Fluoro-naphthalen-1-yl)-piperazine, was produced as follows: A solution of Pd(OAc)2 (0.25 g, 1.11 mmol, 0.1 equiv)) and dicyclohexylphosphino-biphenyl (0.39 g, 1.11 mmol, 0.1 equiv) in toluene (20 mL) was degassed by bubbling N2 gas for 1 h. 1-Bromo-8-fluoro-naphthalene (2.5 g, 11.1 mmol) in toluene (10 mL) and 1-Boc-piperazine (2.5 g, 13.3 mmol, 1.2 equiv) were added followed by NaOtBu (1.6 g, 16.66 mmol, 1.5 equiv). The mixture was stirred at 80° C. for 18 h. The solvent was removed under reduced pressure and the residue was taken in dichloromethane and filtered through a celite pad. The celite was rinsed with dichloromethane and the combined filtrates were concentrated. The residue was purified by silica gel chromatography (20% ethyl acetate in hexane) to give 4-(8-fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester as a dark oil (1.4 g, 38%). 1H NMR (400 MHz, CDCl3): δ 7.60 (d, 1H), 7.50 (d, 1H), 7.40 (m, 1H), 7.10 (m, 2H), 6.95 (d, 1H), 4.50–4.00 (br s, 2H), 3.40–3.20 (m, 4H), 2.80–2.60 (m, 2H), 1.50 (s, 9H). MS (ES+): 331.08 (M+H)+.

Provenance & Evidence