1,4-Dibromobutane → HCID 71765182, compound

Participants

Reaction Conditions

Reaction Steps

A 25 ml round-bottom flask is flushed with nitrogen and charged with 6.9 ml dry THF, 134 mg (5.50 mmol) magnesium turnings and 49 mg (0.20 mmol) cerium(III) chloride. Under stirring, the suspension is cooled to 0° C. Then 378 μl (3.20 mmol) 1,4-dibromobutane is added, the suspension is allowed to reach room temperature, stirred for 30 minutes at this temperature and again cooled to 0° C. Then, a solution of 286 mg (1.00 mmol) 4-(7-fluoro-1-oxo-1,2-dihydro-pyrrolo[1,2-a]pyrazin-3-yl)-benzoic acid methyl ester in 2.3 ml THF is added dropwise. The reaction mixture is stirred for 30 minutes at 0° C. and for 1 hour at room temperature. The reaction mixture is quenched with saturated ammonium chloride solution. To a suspension of 5.73 g (20.0 mmol) 4-(7-fluoro-1-oxo-1,2-dihydro-pyrrolo[1,2-a]pyrazin-3-yl)-benzoic acid methyl ester in 85 ml THF are added 5.42 g (22.0 mmol) and the mixture is stirred for 1 h at ambient temperature under nitrogen. Then 30.5 ml (84.0 mmol) of a 20% solution of methylmagnesium chloride in THF is added dropwise and the reaction mixture is stirred for 30 minutes at room temperature. The reaction mixture is partitioned between ethyl acetate and water. The organic phase is dried over sodium sulfate and evaporated. The residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate as eluent to afford 7-fluoro-3-[4-(1-hydroxy-cyclopentyl)-phenyl]-2H-pyrrolo[1,2-a]pyrazin-1-one as light orange powder; HPLC/MS 2.37 (B), [M+H] 313; 1H NMR (400 MHz, DMSO-d6) δ [ppm] 10.99 (s, 1H), 7.62 (s, 1H), 7.59 (d, J=8.5 Hz, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.48 (dd, J=3.4, 1.9 Hz, 1H), 6.75 (d, J=1.8 Hz, 1H), 4.85 (s, 1H), 1.92-1.80 (m, 6H), 1.80-1.69 (m, 2H).

Provenance & Evidence