4-Fluorobenzylamine → (4-Fluoro-benzyl)-carbamic acid (6R,7aS)-3-oxo-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-6-yl ester

Beteiligte Stoffe

Reaktionsschritte

Diisopropylethylamine (800 mg, 6.2 mmol) and (4-fluorophenyl)methanamine (400 mg, 3.2 mmol) was dropped into a solution of bis(trichloromethyl) carbonate (300 mg, 1 mmol) in anhydrous dichloromethane (30 mL) at −78° C., the mixture was stirred for 2 hours at room temperature. Then (6R,7aS)-6-Hydroxy-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one (example 1, step e) (50 mg, 0.165 mmol) was added into the mixture, the mixture was refluxed for 2 days. The mixture was cooled and poured into water (50 mL), extracted with ethyl acetate (3×30 mL), the organic layers was combined washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=5:1) to yield 25 mg (33%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 7.60 (d, 2H, J=9.3 Hz), 7.29-7.24 (m, 2H), 7.19 (d, 2H, J=8.4 Hz), 7.03 (t, 2H, J=8.7 Hz), 5.38 (t, 1H, J=5.7 Hz), 5.04 (s, 1H), 4.34 (d, 2H, J=5.7 Hz), 4.15 (dd, 1H, J1=13.5 Hz, J2=6.0 Hz), 4.05-4.00 (m, 1H), 3.74 (d, 1H, J=6.9 Hz), 3.2 (d, 1H, J=13.5 Hz), 2.27-2.21 (m, 1H), 1.78-1.63 (m, 1H); LC-MS: 454.1 [M+1]+.

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