반응 #161907

반응 방정식

ammonium hydroxide

N-methylmorpholine

ethyl chloroformate

Boc-Phe-OH

→

#12

수율 82.0%

Nα-(tert-butoxycarbonyl)-L-phenylalaninamide

수율 82.0%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   농축before being concentrated in vacuo
2. 2
   workup.ADDITIONThe residue was diluted with ethyl acetate
3. 3
   세척washed sequentially with 1 N aqueous potassium bisulfate solution, water and brine
4. 4
   건조The organic layer was then dried over sodium sulfate
5. 5
   여과filtered
6. 6
   농축concentrated in vacuo
7. 7
   workup.DISSOLUTIONThe white solid was dissolved (
8. 8
   온도this required heating
9. 9
   workup.STIRRINGwith stirring) in ethyl acetate (about 400 mL)
10. 10
    온도to cool to room temperature
11. 11
    workup.ADDITIONbefore adding hexane (1000 mL)
12. 12
    workup.WAITAfter a few minutes
13. 13
    기타to precipitate from the reaction mixture
14. 14
    여과The solid was collected by filtration
15. 15
    세척washed with heptane (2ט150 mL)
16. 16
    기타dried under vacuum for 18 hours

실험 절차

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).

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