反应详情

Using method analogous to those described for the synthesis of intermediates 1 to 3, the intermediate below was synthesised according to the method described below. 2-piperazinone (2.51 g, 25.07 mmol, commercially available e.g. from Sigma-Aldrich) and triethylamine (4.19 mL, 30.1 mmol) were dissolved in Dichloromethane (DCM) (50 mL). 2,3-dichloro-4-fluorobenzoyl chloride (I33)(6.28 g, 27.6 mmol) dissolved in Dichloromethane (DCM) (50 mL) was added dropwise at 0° C. and the solution allowed to stir to room temperature overnight. The mixture was diluted with Dichloromethane (200 mL) and washed with saturated sodium bicarbonate solution (100 mL). The aqueous phase was extracted with Dichloromethane (3×100 mL) and the combined extracts were washed with water (2×100 mL), brine (100 mL), dried over anhydrous sodium sulfate and concentrated to a crude solid that was triturated with hexane to afford product in 6.94 g. The product was recrystalised from ethanol (Note: slow to come out of solution) to afford the desired product in 5.08 g.

1. customthe intermediate below was synthesised
2. additionwas added dropwise at 0° C.
3. washwashed with saturated sodium bicarbonate solution (100 mL)
4. extractionThe aqueous phase was extracted with Dichloromethane (3×100 mL)
5. washthe combined extracts were washed with water (2×100 mL), brine (100 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated to a crude solid
8. customthat was triturated with hexane
9. customto afford product in 6.94 g
10. customThe product was recrystalised from ethanol (Note: slow to come out of solution)