1-Chloro-2-methylpropyl propanoate → (2-(((4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)butyl)(2-methyl-1-(1-oxopropoxy)propoxy)phosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide

HRID 1489793

Reaktionsgleichung

Reaktionsgleichung von HRID 1489793
[C:1]([O:5][CH:6](Cl)[CH:7]([CH3:9])[CH3:8])(=[O:4])[CH2:2][CH3:3].[C:11]1([NH:17][C:18](=[O:54])[C@H:19]([CH2:50][CH:51]([CH3:53])[CH3:52])[NH:20][C:21](=[O:49])[CH:22]([CH2:31][P:32]([CH2:35][CH2:36][CH2:37][CH2:38][N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:48])([OH:34])=[O:33])[CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>[I-].C([N+](CCCCCC)(CCCCCC)CCCCCC)CCCCC.C(OCC)(=O)C>[C:11]1([NH:17][C:18](=[O:54])[C@H:19]([CH2:50][CH:51]([CH3:52])[CH3:53])[NH:20][C:21](=[O:49])[CH:22]([CH2:31][P:32]([CH2:35][CH2:36][CH2:37][CH2:38][N:39]2[CH2:47][C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40]2=[O:48])([O:34][CH:6]([O:5][C:1](=[O:4])[CH2:2][CH3:3])[CH:7]([CH3:9])[CH3:8])=[O:33])[CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Komponenten

5

Edukt 2

HCID 126610101-Chloro-2-methylpropyl propanoateHCID 57084392(2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide

Produkt 1

HCID 57064548(2-(((4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)butyl)(2-methyl-1-(1-oxopropoxy)propoxy)phosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamideAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 75056Tetrahexylammonium iodideKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

1-Chloroisobutyl propionate (0.20 mL) was added to a mixture of 4 Å molecular sieves (125 mg), tetra-n-hexylammonium iodide (40 mg, 0.083 mmol), and (2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide (50 mg, 0.081 mmol).6The mixture was warmed in an oil bath at 65°-70° C. for 7 h, then allowed to stand at room temperature overnight. The mixture was diluted into ethyl acetate (25 mL) and washed with 2N aqueous hydrochloric acid (25 mL) and saturated aqueous sodium chloride, and the organic layer was dried (sodium sulfate), decanted, and evaporated. The crude product was purified by flash column chromatography on silica gel (3 g) eluting with 20% acetone/dichloromethane to give 19 mg.(32% yield) of (2-(((4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)butyl)(2-methyl-1-(1-oxopropoxy)propoxy)phosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide.

Aufarbeitung

  1. temperaturewas warmed in an oil bath at 65°-70° C. for 7 h
  2. washwashed with 2N aqueous hydrochloric acid (25 mL) and saturated aqueous sodium chloride
  3. dry with materialthe organic layer was dried (sodium sulfate)
  4. customdecanted
  5. customevaporated
  6. customThe crude product was purified by flash column chromatography on silica gel (3 g)
  7. washeluting with 20% acetone/dichloromethane
  8. customto give 19 mg

Quellen und Nachweise

ORD-Eintrag
ord-15281153d9024d7d8e360e612d5177f7
Quelldatensatz
uspto-grants-1997_10
Patentnummer
US05679700

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