反应详情

To a solution of dibenzyl phosphate (2.48 g, 8.91 mmol) in dichloromethane (25 ml) was added N,N-dimethyl formamide (1 drop) followed by oxalyl chloride (0.75 mL, 8.91 mmol). After 2 hours the reaction mixture was concentrated in vacuo. The residue was dissolved in 2-methyltetrahydrofuran (5 mL) and added to a suspension of dehydro-aripiprazole (1.66 g, 3.71 mmol) and potassium t-butoxide (0.92 g, 8.17 mmol) in 2-methyltetrahydrofuran (35 mL) at 0° C. under argon gas, then allowed to gradually warm to room temperature. After stirring overnight the reaction was quenched with water (25 mL) and 28% aq NH3 (15 mL) and stirred for 10 minutes. The reaction mixture was then extracted with ethyl acetate (2×40 mL). The combined organics were washed with water (50 mL) and brine (50 mL) then dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by column chromatography eluting with 5% methanol (1:1 ethyl acetate/dichloromethane) to give the product. The 1H-NMR showed minor impurities still present (impurities not observed by LCMS). Various further purifications were attempted but failed to remove these impurities.

1. concentrationAfter 2 hours the reaction mixture was concentrated in vacuo
2. dissolutionThe residue was dissolved in 2-methyltetrahydrofuran (5 mL)
3. customwas quenched with water (25 mL) and 28% aq NH3 (15 mL)
4. stirringstirred for 10 minutes
5. extractionThe reaction mixture was then extracted with ethyl acetate (2×40 mL)
6. washThe combined organics were washed with water (50 mL) and brine (50 mL)
7. dry with materialthen dried (MgSO4)
8. concentrationconcentrated in vacuo
9. customThe crude mixture was purified by column chromatography
10. washeluting with 5% methanol (1:1 ethyl acetate/dichloromethane)
11. customto give the product
12. customto remove these impurities