3,4-dihydro-2H-pyran → L-Alanyl-L-proline

참여 물질

반응 단계

The compound 1 and 3,4-dihydro-2H-pyran in CH2Cl2 and pyridinium p-toluenesulfonate are stirred at room temperature for 12 h as indicated in the schematic below. Then the solution is diluted with EtOAc and washed with half-saturated brine to remove the catalyst. The solvent is evaporated and the residue is treated with NaOH(1N) and EtOH for 30 min. The solution is acidified with AcOH, and the product is extracted with EtOAc. The EtOAc solution is dried, evaporated to give the THP ether 2. The compound 2, DCC and HOBT in CH2Cl2 are stirred at room temperature for 60 min. Then MEEA-EDA HCI (N-(2-aminoethyl)[2-(2-maleiimidoethoxy)ethoxy]acetamide) and N-methylmorpholine are added. The reaction is stirred for 2 h., and then quenched by addition of AcOH. The precipitate is removed by filtration. The filtrate is washed with diluted HCl, NaHCO3, and dried. The crude product is used for the next step. The crude product is treated with 2N HCI H2O/EtOH 1:1) for 30 min. EtOH is evaporated. The product is extracted with CH2Cl2. The combined CH2Cl2 layers are washed with NaHCO3, and dried. Evaporation of the solvent gives a residue, which is purified by flash column chromatography to afford 3. This compound can be purified further by HPLC on a reverse phase column and lyophilized to produce the modified MMPI.

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