Methyl formate → 1-(1-Benzylpiperidin-4-yl)-2-formyl-3-phenyl-1-propanone

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Reaction Steps

Into a 100 mL 3-neck round-bottom flask was weighed 0.336 g KO-t-Bu and 4 mL anhydrous THF was added. The mixture was cooled with an ice bath under nitrogen, and to it was added a solution of 0.29 g 1-(1-benzylpiperidin-4-yl)-3-phenyl-1-propanone from the last step and 1.80 g methyl formate in 12 mL THF over 5 minute with stirring. After stirring for an additional 15 min, the cooling bath was removed, and the yellowish cloudy mixture was stirred for 2 hours. The mixture was then poured into water, extracted with 4×50 mL ether, 40 mL dichloromethane, and 3×40 mL THF and the combined organic layers were washed with 50 mL each of water and saturated brine, dried over Na2SO4, and concentrated under reduced pressure to give 0.414 g of the title compound as a sticky yellowish solid. This crude product was used without further purification in the next step. RF: 0.59 (EtOAc with 3% (v/v) Et3N and 5% (v/v) MeOH). 1H NMR (500 MHz, DMSO-d6): δ7.97 (s, 1H), 7.20˜7.30 (m, 5H), 7.14˜7.17 (m, 2H), 7.04˜7.09 (m, 3H), 6.85 (s, 1H), 3.45 (s, ˜2H), 2.81˜2.89 (m, 1H), 2.76˜2.80 (m, 2H), 1.97˜2.03 (m, 2H), 1.46˜1.56 (m, 4H). The Ph—CH2—C═ signal was not observed, possibly overlapping with the large water signal. ESI-MS 336.1 (M+H), HPLC A: 2.32 min.

Provenance & Evidence