反应详情

A portion (5.2 g; 20 mmol) of the methyl 4-Boc-piperazine-2-acetate product from the previous step was combined with 60 mL of THF and 60 mL of 1 N NaOH (aqueous) and stirred at room temperature for 6 hours to saponify the methyl ester. The reaction was cooled to 0° C., adjusted to pH 9-10 with 10% HCl(aqueous), and 5.2 g (20 mmol) of FMOC-Cl was added. The reaction was stirred at room temperature for 6 hours, (adding 1 N NaOH (aqueous) to maintain pH=9-10) 1 hour, then acidified with 10% HCl to pH=1. The reaction was extracted twice, the combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo to give 8.56 g of the desired 4-Boc-1-Fmoc-piperazine-2-acetic acid (the compound of formula (XXIV)); 1H NMR (CDCl3) δ1.4 (s, 9), 2.5-3.0 (m, 5), 3.9-4.2 (m, 6), 4.5 (m, 1), 7-25 (t, 4), 7.32 (t, 4), 7.48 (d, 4),7.75 (d, 4).

1. temperatureThe reaction was cooled to 0° C.
2. additionwas added
3. stirringThe reaction was stirred at room temperature for 6 hours
4. extractionThe reaction was extracted twice
5. washthe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo