反応 #4593

反応方程式

L-phenylalanine methyl ester hydrochloride

N-methyl morpholine

N-Methylmorpholine

isobutyl chloroformate

L-pyroglutamic acid

→

L-Pyroglutamyl-L-phenylalanine Methyl Ester

溶媒

EtOAc AcOH

DMF

THF DMF

反応条件

後処理

1. 1
   workup.ADDITIONwas added to the reaction mixture
2. 2
   workup.WAITto proceed at this temperature for 30 minutes
3. 3
   その他at room temperature
4. 4
   ろ過The reaction mixture was then filtered
5. 5
   その他to remove fines
6. 6
   その他the filtrate was evaporated in vacuo
7. 7
   workup.DISSOLUTIONThe resulting yellow liquid was dissolved in 100 ml of ethyl acetate
8. 8
   洗浄the ethyl acetate solution was washed with 5% citric acid saturated with sodium chloride (50 ml) and 5% sodium bicarbonate saturated with NaCl (50 ml)
9. 9
   乾燥The separated organic layer was dried over anhydrous sodium sulfate
10. 10
    その他evaporated in vacuo
11. 11
    その他to yield quantitative amounts of a pale yellow liquid which
12. 12
    その他quenching

実験手順

N-Methylmorpholine (2.02 g, 0.020 mol) and isobutyl chloroformate (2.73 g, 0.020 mol) were added to a solution of L-pyroglutamic acid (2.58 g, 0.020 mol) in 100 ml of THF/DMF (6:1) at -15° C. After a 2 minute coupling period, a mixture of L-phenylalanine methyl ester hydrochloride (4.31 g, 0.020 mol) (suspension) and N-methyl morpholine (2.02 g, 0.020 mol) in 50 ml of DMF was added to the reaction mixture. The reaction was allowed to proceed at this temperature for 30 minutes and then at room temperature for 1 additional hour. The reaction mixture was then filtered to remove fines and the filtrate was evaporated in vacuo to incipient dryness. The resulting yellow liquid was dissolved in 100 ml of ethyl acetate, and the ethyl acetate solution was washed with 5% citric acid saturated with sodium chloride (50 ml) and 5% sodium bicarbonate saturated with NaCl (50 ml). The separated organic layer was dried over anhydrous sodium sulfate and evaporated in vacuo to yield quantitative amounts of a pale yellow liquid which was used directly for the following step. TLC: Rf =0.22 in EtOAc/AcOH (100:1), detected by UV quenching; IR (neat, cm-1) 3300 (NH), 3020-3060 (C6H5), 2860-2960 (alkyl), 1650-1750 (C=O); NMR (Silanor C, δ from TMS) 7.25 (fused s, C6H5 --), 5.5-5.7 and 6.6-6.8 (broad, NH's), 4.6-5.1 (g, --NH--CH--C=O), 3.0-3.2 (q, --CH2 --C6H5), 1.6-2.5 (m, cycl. O=C--CH2 --CH2).

出典