Dimethyl malonate → HCID 86700878, compound

Participants

Reaction Steps

To a solution of dimethyl malonate (0.47 mL, 4.1 mmol) in anhydrous dimethyl acetamide (5.6 mL) cooled in an ice-water bath was added NaH (60% dispersion in mineral oil, 163 mg, 4.1 mmol) portion-wise and the reaction was let stir at rt for 30 min until homogeneous. To this was added 1-(4-bromophenyl)-4-(iodomethyl)-7-oxabicyclo[2.2.1]heptane (440 mg, 1.12 mmol) and the reaction was stirred in a microwave reactor at 150° C. for 45 min. The resulting yellow reaction mixture was quenched with a saturated aqueous NH4Cl solution and extracted with EtOAc. The organic phase was dried over MgSO4, filtered and concentrated by rotary evaporation in vacuo to afford a crude yellow oil. Purification of the crude material by column chromatography (40 g silica gel, 0-30% EtOAc:Hept, monitor 225 nm) afforded 108 mg (28%) of methyl 3-(4-(4-bromophenyl)-7-oxabicyclo[2.2.1]heptan-1-yl)propanoate (decarboxylated material) as a clear yellow film and 245 mg (55%) of the title compound as a clear yellow film. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.54-1.79 (m, 6H), 2.06-2.16 (m, 2H), 2.39 (d, J=7.1 Hz, 2H), 3.66 (s, 6H), 3.73 (t, J=7.1 Hz, 1H), 7.27 (d, J=8.6 Hz, 2H), 7.54 (d, J=8.6 Hz, 2H). ESI-MS m/z: 399.0 [M+H]+, retention time 1.59 min (condition E).

Provenance & Evidence