tert-Butyl piperazine-1-carboxylate → HCID 69417977, Verbindung

A third intermediate compound, 1-(8-Chloro-naphthalen-1-yl)-piperazine, was produced as follows: To an oven dried flask, 1-boc-piperazine (1.2 g, 6.47 mmol), NaOtBu (0.724 g, 7.54 mmol), Pd(OAc)2 (0.12 g, 0.539 mmol), 2-(di-cyclohexylphosphino)biphenyl (0.12 g, 0.539 mmol), toluene (15 mL) and 1-bromo-8-chloro-naphthalene (1.3 g, 5.39 mmol) were added. While stirring the reaction mixture at room temperature, the air in the flask was removed and refilled with N2. This process was repeated three times. The reaction mixture was stirred for 3 h at 80–90° C. Diethyl ether was added at room temperature and the mixture was filtered through a pad of silica gel. The brown oily material was purified by chromatography on silica, eluting with hexanes:chloroform (1:1) and then changing to 100% chloroform, to give 4-(8-chloro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester as an oil (1.35 g, 72%). 1H-NMR (400 MHz, CDCl3) δ 7.73 (dd, 1H), 7.56 (dd, 1H), 7.52 (dd, 1H), 7.42 (t, 1H), 7.34 (t, 1H), 7.18 (dd, 1H), 4.16 (s, 2H), 3.38 (s, 2H), 3.22 (m, 2H), 2.76 (m, 2H), 1.45 (s, 9H).

1. customTo an oven dried flask
2. customthe air in the flask was removed
3. additionrefilled with N2
4. stirringThe reaction mixture was stirred for 3 h at 80–90° C
5. additionDiethyl ether was added at room temperature
6. filtrationthe mixture was filtered through a pad of silica gel
7. customThe brown oily material was purified by chromatography on silica
8. washeluting with hexanes:chloroform (1:1)

ORD-Eintrag

ord-93ddb4eb12e94bf5b19faf87237631af

Quelldatensatz

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07160888B2