تفاعل #47275

معادلة التفاعل

(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

المردود 147.2%

المذيبات

ethanol

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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.

المصدر