4-Methylmorpholine → 2-(4-methoxybenzylthio)-pentanoyl-(L)-homophenylalanyl-(L)-phenylalanine t-butyl ester

HRID 276113

Reaction equation

HRID 276113 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][S:8][CH:9]([CH2:25][CH2:26][CH3:27])[C:10]([NH:12][C@H:13]([C:22](O)=[O:23])[CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:11])=[CH:5][CH:4]=1.Cl.[C:31]([O:35][C:36](=[O:46])[C@H:37]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[NH2:38])([CH3:34])([CH3:33])[CH3:32].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.OC1C2N=NNC=2C=CC=1>ClCCl.CCCCCC.C(OCC)(=O)C>[C:31]([O:35][C:36](=[O:46])[C@H:37]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[NH:38][C:22](=[O:23])[C@H:13]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[NH:12][C:10](=[O:11])[CH:9]([S:8][CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:29][CH:28]=1)[CH2:25][CH2:26][CH3:27])([CH3:34])([CH3:32])[CH3:33]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11459563L-Phenylalanine, 1,1-dimethylethyl ester, hydrochloride (1:1)HCID 229508272-(4-methoxybenzylthio)-pentanoyl-(L)-homophenylalanineHCID 178418300HCID 178418300, compound

Product 1

HCID 544815592-(4-methoxybenzylthio)-pentanoyl-(L)-homophenylalanyl-(L)-phenylalanine t-butyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21226206Ethyl acetate hexaneSolvent2×

Procedure

Combine 2-(4-methoxybenzylthio)-pentanoyl-(L)-homophenylalanine (0.14 g, 0.34 mmol), (L)-phenylalanine t-butyl ester hydrochloride salt (0.174 g, 68 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.13 g, 0.67 mmol) in dichloromethane (5 mL). Add N-methylmorpholine (0.1 mL, 1.01 mmol) and hydroxybenzotriazole (0.091 g, 0.67 mmol). After 3 hours, after 1 hour, partition the reaction mixture between methyl t-butyl ether and an aqueous 5% sulfuric acid solution. Separate the layers, extract the organic layer with a saturated sodium bicarbonate solution and then brine. Dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with 3/1 hexane/ethyl acetate and then 1/1 hexane/ethyl acetate to give the title compound: Rf=0.45 (silica gel, 1/1 ethyl acetate/hexane).

Workup

  1. waitafter 1 hour
  2. custompartition the reaction mixture between methyl t-butyl ether
  3. customSeparate the layers
  4. extractionextract the organic layer with a saturated sodium bicarbonate solution
  5. dry with materialDry over Na2SO4
  6. filtrationfilter
  7. customevaporate in vacuo
  8. customto give a residue

Sources & evidence

ORD record
ord-3efab06d140545abb74c0a66e8be5fb3
Source dataset
uspto-grants-2002_03
Patent number
US06352976B1

Linked notes

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