tert-butyl (2S,3R)-1-((2S,4R)-2-((1R,2S)-1-(1-(fluoromethyl)cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-ylcarbamate → HCID 71005415, compound

HRID 1481656Notes

Reaction equation

HRID 1481656 reaction equation
[C:1]([O:5][C:6](=[O:45])[NH:7][C@@H:8]([C@H:36]([CH3:44])[CH2:37][CH:38]([CH3:43])[CH2:39][CH2:40]C=C)[C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[C:17](=[O:35])[NH:18][C@:19]1([C:24](=[O:34])[NH:25][S:26]([C:29]2([CH2:32][F:33])[CH2:31][CH2:30]2)(=[O:28])=[O:27])[CH2:21][C@H:20]1[CH:22]=[CH2:23])=[O:10])([CH3:4])([CH3:3])[CH3:2]>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:1]([O:5][C:6](=[O:45])[NH:7][C@@H:8]1[C:9](=[O:10])[N:11]2[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]2[C:17](=[O:35])[NH:18][C@:19]2([C:24](=[O:34])[NH:25][S:26]([C:29]3([CH2:32][F:33])[CH2:31][CH2:30]3)(=[O:27])=[O:28])[CH2:21][C@H:20]2[CH:22]=[CH:23][CH2:40][CH2:39][CH:38]([CH3:43])[CH2:37][C@H:36]1[CH3:44])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 1

HCID 86683251tert-butyl (2S,3R)-1-((2S,4R)-2-((1R,2S)-1-(1-(fluoromethyl)cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-ylcarbamate

Product 1

HCID 71005415HCID 71005415, compoundYield 27.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

A solution of tert-butyl((2S,3R)-1-((2S,4R)-2-(((1R,2S)-1-(((1-(fluoromethyl)cyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate (7.5 g, 22.84 mmol) in DCE (2855 ml) was spurged with nitrogen for 30 min. and then Hoveyda-Grubbs Catalyst 2nd Generation (0.718 g, 1.142 mmol) was added and the reaction was heated to 80° C. for 2 hrs. The reaction was concentrated and purified by flash chromatography on silica gel (20-60% Acetone in hexanes) to give tert-butyl((2R,6S,7R,13aS,14aR,16aS,Z)-14a-(((1-(fluoromethyl)cyclopropyl)sulfonyl)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 (4 g, 6.36 mmol, 27.9% yield). MS: MS m/z 629.3 (M++1).

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by flash chromatography on silica gel (20-60% Acetone in hexanes)

Sources & evidence

ORD record
ord-2e3f9a4edb244a0dbcce60d59f959011
Source dataset
uspto-grants-2016_08
Patent number
US09409943B2

Reaction notes

Loading…