7-Hydroxymethyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-1-one → 7-Formyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-1-one

7-hydroxymethyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-1-one (20 g, 96 mmol) was dissolved in chloroform (300 ml), to which was added active manganese dioxide (80 g, 920 mmol) in several portions, and the resultant was stirred at room temperature for 4 hours. The insoluble matter was removed by filtration under reduced pressure, the filtrate was concentrated under reduced pressure and the resulting crude product was recrystallized from toluene to give 12.31 g of 7-formyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-1-one as yellow needle-like crystal (yield: 62%). Melting point of the product was 73°-75° C. 10% aqueous sodium hydroxide (50 ml) was added to the aldehyde (5 g, 24 mmol) and stirred overnight at room temperature. The reaction solution was acidified with 10% dilute hydrochloric acid, then extracted with methylene chloride, washed with water, dried, and solvent was distilled off to give a crude crystal (4.78 g). The crude crystal was recrystallized from ethyl acetate/hexane to give 7-formyl-4-isopropyl-2-hydroxy-2,4,6-cycloheptatrien-1-one as a colorless needle-like crystal (yield: quantitative). This compound showed melting point of 76° C., which is identical to that described in the literature (Sci. Repts. Tohoku Univ., I, 37, 367 (1953)]. The compound (1.94 g, 10 mmol) was dissolved in tetrahydrofuran (20 ml), to which was added dropwise 2M phenyl lithium solution (5.2 ml, ca 10 mmol) in a nitrogen atmosphere while cooling to -78° C. The resultant was stirred for 10 minutes. An aqueous saturated sodium chloride was added to the reaction solution, and the resultant was extracted with methylene chloride, dried and the solvent was distilled off. The residue was purified by silica gel column chromatography to give 1.95 g of 7-(α-hydroxybenzyl)-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-1-one as brown oil (yield: 71%). The compound (1 g, 3.7 mmol) and 1-(4-chlorobenzhydryl)piperazine (1.27 g, 4.4 mmol) were heated and refluxed in xylene (20 ml) for 2 hours, solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography [(ethyl acetate/hexane (1:2)] to give 1.71 g of 7-{1-[4-(4-chlorobenzhydryl)piperazinomethyl]-α-phenyl}-4-isopropyl-2-hydroxyl-2,4,6-cycloheptatrien-1-one (yield: 86%).

1. customThe insoluble matter was removed by filtration under reduced pressure
2. concentrationthe filtrate was concentrated under reduced pressure
3. customthe resulting crude product was recrystallized from toluene

ORD record

ord-a9fcf07167a944fd8ebf9ae72505f2fb

Source dataset

uspto-grants-1997_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05594144