反应详情

温度

0 °C

A solution of triphenylphosphine (430 mg, 1.64 mmol) in anhydrous DMAC (4 ml) at 0° C. was treated dropwise under N2 with bromine (84 μL, 1.64 mmol). The solution was stirred at 0° C. for 15 minutes, treated with the compound obtained in Example 2 (100 mg, 0.76 mmol), and stirred at 25° C. for 1.7 hours to give the compound of Formula IIIA. This solution was treated with diethyl p-aminobenzoyl-L-glutamate (194 mg, 0.603 mmol), stirred at 25° C. for 17 hours and poured into ice water (40 ml). The resulting solution (pH 2) was filtered to remove triphenylphosphine oxide, adjusted to pH 6.8 with 50% NaOH, and cooled in an ice bath. The precipitate of crude product (VII; R=H, R1 =C2H5) was collected by centrifugation, washed with H2O and dried in vacuo (P2O5); yield 136 mg (73%). The retention time (HPLC) and rf value (TLC) of this product were identical to those obtained from the analytical sample obtained in Part A of this example. Mass spectrum: m/e 496 (M+1)+.

1. stirringstirred at 25° C. for 1.7 hours
2. customto give the compound of Formula IIIA
3. stirringstirred at 25° C. for 17 hours
4. filtrationThe resulting solution (pH 2) was filtered
5. customto remove triphenylphosphine oxide
6. temperaturecooled in an ice bath
7. customThe precipitate of crude product (VII; R=H, R1 =C2H5) was collected by centrifugation
8. washwashed with H2O
9. dry with materialdried in vacuo (P2O5)
10. customthose obtained from the analytical sample