1,2-Dichloroethane → Methyl N-{[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}-3-methyl-L-valyl-(4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}-L-prolinate

HRID 1511548Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1511548
Cl.[CH:2]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][N:7]([C:13]([O:15][C@@H:16]1[CH2:20][C@@H:19]([C:21]([O:23][CH3:24])=[O:22])[NH:18][CH2:17]1)=[O:14])[CH2:8]2)=[CH2:3].[CH3:25][C:26]([CH3:44])([CH2:40][CH2:41][CH:42]=[CH2:43])[CH2:27][O:28][C:29]([NH:31][C@H:32]([C:37](O)=[O:38])[C:33]([CH3:36])([CH3:35])[CH3:34])=[O:30].CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.CCOCC>[CH3:25][C:26]([CH3:44])([CH2:40][CH2:41][CH:42]=[CH2:43])[CH2:27][O:28][C:29]([NH:31][C@H:32]([C:37]([N:18]1[CH2:17][C@H:16]([O:15][C:13]([N:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH:2]=[CH2:3])[CH2:8]2)=[O:14])[CH2:20][C@H:19]1[C:21]([O:23][CH3:24])=[O:22])=[O:38])[C:33]([CH3:34])([CH3:35])[CH3:36])=[O:30]

Komponenten

8

Edukt 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 45379499(S)-2-((((2,2-Dimethylhex-5-en-1-yl)oxy)carbonyl)amino)-3,3-dimethylbutanoic acidHCID 45379932(3R,5S)-5-(Methoxycarbonyl)pyrrolidin-3-yl 4-vinyl-1,3-dihydro-2H-isoindole-2-carboxylate Hydrochloride

Produkt 1

HCID 45379615Methyl N-{[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}-3-methyl-L-valyl-(4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}-L-prolinateAusbeute 50,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of (3R,5S)-5-(methoxycarbonyl)pyrrolidin-3-yl 4-vinyl-1,3-dihydro-2H-isoindole-2-carboxylate hydrochloride (5.0 g, 14.2 mmol) and N-{[(2,2-dimethylhex-5-enyl)oxy]carbonyl}-3-methyl-L-valine (4.0 g, 14.2 mmol) in DMF (20 ml) at RT was added DIPEA (2.5 mL, 14.2 mmol), EDC (5.5 g, 28.4 mmol), and HOAt (1.9 g, 14.2 mmol). After 18 h the reaction mixture was poured into Et2O, and extracted with 1 N HCl. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with 1 N HCl, water, NaHCO3, and brine. The organic layer was dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified on silica (30% EtOAc in hexanes) to yield 4.2 g of the title compound as a thick oil. LRMS (ESI) m/z 584.4 [(M+H)+; calcd for C32H46N3O7: 584.3].

Aufarbeitung

  1. extractionextracted with 1 N HCl
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic layers were washed with 1 N HCl, water, NaHCO3, and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. customthe solvent was removed in vacuo
  6. customThe crude product was purified on silica (30% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-4211c4f4ebba4c2c97e606d9db86c54c
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08216999B2

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