Lithium Hydroxide → 1-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide

HRID 1865719Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1865719
O.[CH3:2][N:3]1[CH2:10][CH2:9][CH2:8][C@H:4]1[C:5]([OH:7])=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:53]/[C:54](=[CH:60]\[C@@H:61]([N:65]([CH3:74])[C:66](=[O:73])[C@H:67]([C:69]([CH3:72])([CH3:71])[CH3:70])[NH2:68])[CH:62]([CH3:64])[CH3:63])/[C:55]([O:57]CC)=[O:56].[OH-].[Li+]>ClCCl.CO.ClCCl.O.O1CCCC1.O>[CH3:2][N:3]1[CH2:10][CH2:9][CH2:8][C@H:4]1[C:5]([NH:68][C@H:67]([C:66]([N:65]([C@@H:61]([CH:62]([CH3:64])[CH3:63])/[CH:60]=[C:54](/[C:55]([OH:57])=[O:56])\[CH3:53])[CH3:74])=[O:73])[C:69]([CH3:71])([CH3:72])[CH3:70])=[O:7]

Komponenten

11

Edukt 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11120545ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoateHCID 162119581-Methyl-L-proline--water (1/1)

Produkt 1

HCID 115963751-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamideAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittelHCID 21908982Water methylene chlorideLösungsmittel

Versuchsvorschrift

To a solution of N-methyl-L-proline monohydrate (0.26 g, 1.79 mmol) and benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (1.4 g, 2.69 mmol) in anhydrous dichloromethane (3.0 ml) at 25° C. is added diisopropylethylamine (0.63 ml, 3.62 mmol) under an inert atmosphere. To this solution is added a solution of ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.39 g, 1.27 mmol, WO 99/32509) in anhydrous dichloromethane (2.0 ml). The resulting reaction mixture is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo. The residue (300 mg, 0.78 mmol) is dissolved in methanol (6.85 ml), water (1.8 ml) and tetrahydrofuran (3.25 ml). To this reaction mixture is added aqueous lithium hydroxide solution (3.54 ml, 3.54 mol) The resulting mixture is stirred at room temperature overnight. The reaction mixture is diluted with dichloromethane/water. The organic layer is washed with citric acid, brine, dried over sodium sulfate and filtered. The solvent is removed in vacuo, and the residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile) to give the product as a yellow oil, 0.08 g (28% yield). MS: m/z 396.28 (M+1)

Aufarbeitung

  1. customThe resulting reaction mixture
  2. customThe reaction mixture is evaporated in vacuo
  3. stirringis stirred at room temperature overnight
  4. washThe organic layer is washed with citric acid, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent is removed in vacuo
  8. customthe residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile)

Quellen und Nachweise

ORD-Eintrag
ord-d3dcd8dbf5dc4e9887bcbea06143be5d
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07626023B2

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