反应详情

To a solution of Boc-Phe-OH (30.1 g, 113 mmol, 1 eq.) in tetrahydrofuran (378 mL, 0.3 M) cooled to −10° C. were added N-methylmorpholine (13.6 mL, 124 mmol, 1.09 eq.), and ethyl chloroformate (11.8 mL, 124 mmol, 1.09 eq.). After 20 minutes, a 30% aqueous ammonium hydroxide solution (45 mL, 350 mmol, 3.1 eq.) was added. The mixture was stirred at room temperature for 18 hours before being concentrated in vacuo. The residue was diluted with ethyl acetate and washed sequentially with 1 N aqueous potassium bisulfate solution, water and brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. The white solid was dissolved (this required heating with stirring) in ethyl acetate (about 400 mL); the solution was then allowed to cool to room temperature before adding hexane (1000 mL). After a few minutes, a white material started to precipitate from the reaction mixture. The solid was collected by filtration, washed with heptane (2ט150 mL), and dried under vacuum for 18 hours to give #12 (24.50 g, 82%) as a solid. LC-MS: m/z 263.2 [M−H+], 309.2 [M+HCO2−], retention time=1.85 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, major rotamer: δ 7.35 (br s, 1H), 7.22-7.30 (m, 5H), 7.00 (br s, 1H), 6.78 (d, J=8.6 Hz, 1H), 4.09 (ddd, J=10, 9, 4.5 Hz, 1H), 2.95 (dd, J=13.8, 4.4 Hz, 1H), 2.72 (dd, J=13.7, 10.1 Hz, 1H), 1.30 (s, 9H).

1. concentrationbefore being concentrated in vacuo
2. additionThe residue was diluted with ethyl acetate
3. washwashed sequentially with 1 N aqueous potassium bisulfate solution, water and brine
4. dry with materialThe organic layer was then dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. dissolutionThe white solid was dissolved (
8. temperaturethis required heating
9. stirringwith stirring) in ethyl acetate (about 400 mL)
10. temperatureto cool to room temperature
11. additionbefore adding hexane (1000 mL)
12. waitAfter a few minutes
13. customto precipitate from the reaction mixture
14. filtrationThe solid was collected by filtration
15. washwashed with heptane (2ט150 mL)
16. customdried under vacuum for 18 hours