1H-Isoindole-1,3(2H)-dione, 2-(bromomethyl)- → HCID 67406928, compound

Participants

Reaction Conditions

Reaction Steps

Lithium diisopropylamide solution (1.8M in hexane, 6 ml, 10 mmol) was provided in absolute tetrahydrofuran (10 ml). The solution was cooled to −78° C. After this temperature was reached, 4-(dimethylamino)-4-phenylcyclohexanone (1.1 g, 5 mmol), dissolved in dry THF (5 ml), was added in drops within 1 min. The batch was left for 30 min at −78° C. Then, N-(bromomethyl)phthalimide (3.6 ml, 15 mmol), dissolved in dry THF (20 ml), was added in drops within 1 min. The reaction mixture was stirred for 1 h at −78° C., then the cooling was removed. After room temperature was reached, the batch was stirred for a further 18 h. For work up the batch was carefully mixed with water (1 ml), then saturated NH4Cl solution (40 ml) was added. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (3×30 ml). The combined organic phases were washed with saturated NH4Cl solution (1×40 ml). The organic phases were then mixed with 1N HCl (50 ml) and thoroughly shaken out. The acid aqueous phase was separated and the organic phase was washed with water (2×20 ml). The combined aqueous phases were washed with ethyl acetate (1×30 ml). The aqueous solution was then placed on 2N NaOH (70 ml). An oil separated out of the alkaline solution. The formed mixture was extracted with ethyl acetate (3×30 ml). The combined organic phases were dried over Na2SO4 and then concentrated to low volume. One of the two possible diastereoisomers of the ketone was isolated from the obtained residue (2 g) with a yield of 223 mg (12%) by means of chromatographic purification [silica gel 60 G (50 g); cyclohexane/ethyl acetate 1:10 (700 ml)].

Provenance & Evidence