(1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate → (2R,6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-hydroxy-5,16-dioxo-2,3,5,6,7,8,9,11,13a,14,14a, 15,16,16a-tetradecahydro-1H-cyclopropa(e)pyrrolo[2,1-i][1,7,10]oxadiazacyclopentadecine-14a-carboxylate

HRID 1171951Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1171951
[CH2:1]([O:4][CH2:5][CH2:6][CH2:7][C@H:8]([NH:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[C:17]([NH:19][C@:20]1([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:22][C@H:21]1C=C)=[O:18])=[O:10])[CH:2]=[CH2:3]>C1(C)C=CC=CC=1.ClC1C=CC(OC(C)C)=C(C=1)C=[Ru](Cl)(Cl)C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C>[C:34]([O:33][C:31]([NH:30][C@H:8]1[CH2:7][CH2:6][CH2:5][O:4][CH2:1][CH:2]=[CH:3][C@@H:21]2[CH2:22][C@@:20]2([C:25]([O:27][CH2:28][CH3:29])=[O:26])[NH:19][C:17](=[O:18])[C@@H:12]2[CH2:13][C@@H:14]([OH:16])[CH2:15][N:11]2[C:9]1=[O:10])=[O:32])([CH3:36])([CH3:37])[CH3:35]

Komponenten

4

Edukt 1

HCID 70295348(1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate

Produkt 1

HCID 68655365(2R,6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-hydroxy-5,16-dioxo-2,3,5,6,7,8,9,11,13a,14,14a, 15,16,16a-tetradecahydro-1H-cyclopropa(e)pyrrolo[2,1-i][1,7,10]oxadiazacyclopentadecine-14a-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178425459HCID 178425459, VerbindungKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
68 °C

Versuchsvorschrift

(1R,2S)-ethyl 1-((2S,4R)-1-((S)-5-(allyloxy)-2-(tert-butoxycarbonylamino)pentanoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate (3.55 g, 6.78 mmol) in toluene (750 mL) was degassed by bubbling a stream of nitrogen through the reaction for 1 hr at rt. (5-chloro-2-isopropoxybenzylidene)(1,3-dimesitylimidazolidin-2-yl)ruthenium(V)chloride (0.090 g, 0.14 mmol) was added to the mixture and the mixture was heated to 68° C. (oil bath) and stirred at this temperature for 4 hrs. After removal of solvent, the residue was purified by chromatography (Ethyl acetate:MeOH=40:1) to give (2R,6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-hydroxy-5,16-dioxo-2,3,5,6,7,8,9,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa(e)pyrrolo[2,1-i][1,7,10]oxadiazacyclopentadecine-14a-carboxylate as off white solid (0.84 g, 25%). MS: Calcd.: 495; Found: [M+H]+ 496. 1H NMR (400 MHz, d6-DMSO) δ8.42 (s, 1H), 6.89 (d, J=7.6 Hz, 1H), 5.48-5.60 (m, 2H), 5.10 (d, J=3.6 Hz, 1H), 4.41 (s, 1H), 4.27 (m, 2H), 4.17 (m, 1H), 4.02 (m, 2H), 3.72 (m, 2H), 3.62 (m, 1H), 3.35 (m, 1H), 3.28 (m, 1H), 2.42 (m, 1H), 1.98 (m, 2H), 1.78 (m, 1H), 1.62 (m, 1H), 1.52 (m, 2H), 1.42 (m, 2H), 1.36 (s, 9H), 1.13 (t, J=7.2 Hz, 3H).

Aufarbeitung

  1. customby bubbling a stream of nitrogen
  2. customthrough the reaction for 1 hr at rt
  3. customAfter removal of solvent
  4. customthe residue was purified by chromatography (Ethyl acetate:MeOH=40:1)

Quellen und Nachweise

ORD-Eintrag
ord-b13518d7dd9c476a8da94493e2f0f263
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07829665B2

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