反应详情

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0 °C

To a solution of 1,1-dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate (D23) (100 mg, 0.31 mmol) in DCM (5 ml) was added saturated aqueous NaHCO3 solution (5 ml) and the mixture stirred vigorously for 10 min at 0° C. The mixture was allowed to stand and a solution of phosgene in toluene (0.327 ml, 20% in toluene, 0.63 mmol) was injected into the DCM layer of the reaction mixture. The mixture was stirred for a further 10 min and the DCM layer was separated and the aqueous extracted with DCM. The combined organics were dried and concentrated to give a colourless oil. This whole was dissolved in 1,2-DCE (5 ml) and 4-(4-fluorophenyl)piperidine hydrochloride (74 mg, 0.34 mmol) and triethylamine (0.083 ml, 0.63 mmol) were added. The mixture was heated to 120° C. in a microwave reactor for 30 minutes. The reaction mixture was diluted with DCM/water and the organic layer separated, dried (Na2SO4) and concentration gave a crude colourless oil (189 mg). Column chromatography eluting with 0-10% EtOAc/petrol gave the title compound as a colourless oil (156 mg), MS (ES): MH+ 525.3.

1. stirringThe mixture was stirred for a further 10 min
2. customthe DCM layer was separated
3. extractionthe aqueous extracted with DCM
4. customThe combined organics were dried
5. concentrationconcentrated
6. customto give a colourless oil
7. temperatureThe mixture was heated to 120° C. in a microwave reactor for 30 minutes
8. customthe organic layer separated
9. customdried
10. concentration(Na2SO4) and concentration
11. customgave a crude colourless oil (189 mg)
12. washColumn chromatography eluting with 0-10% EtOAc/petrol