L-Pyroglutamic Acid → L-Pyroglutamyl-L-phenylalanine Methyl Ester

HRID 4497

반응식

HRID 4497 반응식
CN1CCOCC1.ClC(OCC(C)C)=O.[NH:16]1[C:20](=[O:21])[CH2:19][CH2:18][C@H:17]1[C:22]([OH:24])=O.Cl.[CH3:26][O:27][C:28](=[O:38])[C@H:29]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[NH2:30]>C1COCC1.CN(C=O)C.CN(C=O)C.CCOC(C)=O.CC(O)=O>[CH3:26][O:27][C:28](=[O:38])[C@H:29]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[NH:30][C:22](=[O:24])[C@@H:17]1[CH2:18][CH2:19][C:20](=[O:21])[NH:16]1

참가 물질

8

반응물 4

HCID 7405L-Pyroglutamic AcidHCID 79724-Methylmorpholine2회HCID 62365Isobutyl chloroformateHCID 75736Methyl L-phenylalaninate hydrochloride

생성물 1

HCID 12378871L-Pyroglutamyl-L-phenylalanine Methyl Ester

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 21974620tetrahydrofuran N,N-dimethylformamide용매HCID 22609514Ethyl acetate acetate용매

실험 절차

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).

후처리

  1. additionwas added to the reaction mixture
  2. waitto proceed at this temperature for 30 minutes
  3. customat room temperature
  4. filtrationThe reaction mixture was then filtered
  5. customto remove fines
  6. customthe filtrate was evaporated in vacuo
  7. dissolutionThe resulting yellow liquid was dissolved in 100 ml of ethyl acetate
  8. washthe 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. dry with materialThe separated organic layer was dried over anhydrous sodium sulfate
  10. customevaporated in vacuo
  11. customto yield quantitative amounts of a pale yellow liquid which
  12. customquenching

출처 및 근거

ORD 기록
ord-c4b5968c16f543fc8c35e4b753328296
출처 데이터셋
uspto-grants-1988_02
특허 번호
US04726941

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