反应详情

To a stirred mixture of (3R,4S)-piperidine-1,3,4-tricarboxylic acid 1-benzyl ester 3-methyl ester (0.554 g, 0.00172 mol) in N,N-dimethylformamide (8.500 mL, 0.1098 mol) was added 3-methyl-4-piperazin-1-ylbenzonitrile dihydrochloride (0.6146 g, 0.002241 mol), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (1.017 g, 0.001896 mol), and, N,N-diisopropylethylamine (1.509 mL, 0.008620 mol). The reaction mixture was stirred overnight at room temp. Reaction quenched with KH2PO4(sat solution). Layers separated and aq layer extracted with ethyl acetate 3×. Organic layers were washed with brine and dried over magnesium sulfate. Filtered and concentrated. The residue was purified by Combiflash with 40-70% EtOAc/Hex to give the product (75% in yield). MS (ESI): (M+H)+=505.

1. customReaction
2. customquenched with KH2PO4(sat solution)
3. customLayers separated
4. extractionaq layer extracted with ethyl acetate 3×
5. washOrganic layers were washed with brine
6. dry with materialdried over magnesium sulfate
7. filtrationFiltered
8. concentrationconcentrated
9. customThe residue was purified by Combiflash with 40-70% EtOAc/Hex
10. customto give
11. customthe product (75% in yield)