반응 #47275

반응 방정식

(E)-4-bromo-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester

(L)-leucine methyl ester hydrochloride salt

sodium bicarbonate

→

(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester

수율 147.2%

용매

ethanol

반응 조건

후처리

1. 1
   온도The resulting cloudy solution was heated
2. 2
   온도to reflux
3. 3
   기타approx. 500 mL of solvent was removed via a Dean Stark trap
4. 4
   온도before reflux
5. 5
   workup.WAITwas continued overnight
6. 6
   workup.ADDITIONTo this solution was added glacial acetic acid (200 mL)
7. 7
   온도the solution was heated
8. 8
   온도to reflux for an additional 2 h
9. 9
   workup.ADDITIONmethyl t-butyl ether (2.7 L) and water (2 L) were added
10. 10
    기타The mixture was separated
11. 11
    세척the organic phase washed with a 20% sodium chloride solution (2 L)
12. 12
    기타The solution was evaporated
13. 13
    workup.ADDITIONthe residue treated with toluene (2 L)
14. 14
    기타evaporated again

실험 절차

To a solution of (L)-leucine methyl ester hydrochloride salt (152.6 g, 0.840 mol) in ethanol (200 proof denatured, 2500 mL) was added sodium bicarbonate (115.3 g, 1.37 mol) at room temperature and the resulting mixture stirred for 15 min. To this mixture was added (E)-4-bromo-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester (87.7% pure by HPLC, 200 g, 0.549 mol). The resulting cloudy solution was heated to reflux and approx. 500 mL of solvent was removed via a Dean Stark trap before reflux was continued overnight. To this solution was added glacial acetic acid (200 mL) and the solution was heated to reflux for an additional 2 h. The reaction mixture was cooled to room temperature and methyl t-butyl ether (2.7 L) and water (2 L) were added. The mixture was separated and the organic phase washed with a 20% sodium chloride solution (2 L). The solution was evaporated, the residue treated with toluene (2 L) and evaporated again to give (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (83.3% pure by HPLC, 273 g) as a dark orange oil.

출처