tert-butyl ((2S,3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate → tert-Butyl ((2R,6S,7R,13 aS,14aR,16aS,Z)-14a-((cyclopropylsulfonyl)carbamoyl)-2-hydroxy-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate

HRID 1852124

Reaktionsgleichung

Reaktionsgleichung von HRID 1852124
[CH:1]1([S:4]([NH:7][C:8]([C@@:10]2([NH:15][C:16]([C@@H:18]3[CH2:22][C@@H:21]([OH:23])[CH2:20][N:19]3[C:24](=[O:43])[C@@H:25]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C@H:26]([CH3:34])[CH2:27][CH:28]([CH3:33])[CH2:29][CH2:30]C=C)=[O:17])[CH2:12][C@H:11]2[CH:13]=[CH2:14])=[O:9])(=[O:6])=[O:5])[CH2:3][CH2:2]1>ClCCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[C:38]([O:37][C:36](=[O:42])[NH:35][C@@H:25]1[C:24](=[O:43])[N:19]2[CH2:20][C@H:21]([OH:23])[CH2:22][C@H:18]2[C:16](=[O:17])[NH:15][C@:10]2([C:8](=[O:9])[NH:7][S:4]([CH:1]3[CH2:2][CH2:3]3)(=[O:6])=[O:5])[CH2:12][C@H:11]2[CH:13]=[CH:14][CH2:30][CH2:29][CH:28]([CH3:33])[CH2:27][C@H:26]1[CH3:34])([CH3:41])([CH3:39])[CH3:40]

Komponenten

4

Edukt 1

HCID 89550268tert-butyl ((2S,3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate

Produkt 1

HCID 89550183tert-Butyl ((2R,6S,7R,13 aS,14aR,16aS,Z)-14a-((cyclopropylsulfonyl)carbamoyl)-2-hydroxy-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamateAusbeute 77,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumKatalysatorHCID 111,2-DichloroethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of tert-butyl ((2S,3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate (9.5 g, 15.21 mmol) in DCE (2500 ml) was sparged with nitrogen for 30 min. and then Hoveyda-Grubbs Catalyst 2nd Generation (0.574 g, 0.912 mmol) was added and the reaction heated to 80° C. for 2 hrs then cooled down to 45° C. and stirred for 2 days. The reaction was concentrated and purified by flash chromatography on silica gel (20-60% Acetone in hexanes) to give the product tert-Butyl((2R,6S,7R,13aS,14aR,16aS,Z)-14a-((cyclopropylsulfonyl)carbamoyl)-2-hydroxy-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate (7 g). MS: MS m/z 597.35 (M++1).

Aufarbeitung

  1. temperaturethen cooled down to 45° C.
  2. concentrationThe reaction was concentrated
  3. custompurified by flash chromatography on silica gel (20-60% Acetone in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-00c1b76613ac4259bf3b7b49463b4cb4
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08957203B2

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