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 1852122Notes

Reaction equation

HRID 1852122 reaction equation
[F:1][CH2:2][C:3]1([S:6]([NH:9][C:10]([C@@:12]2([NH:17][C:18]([C@@H:20]3[CH2:24][C@@H:23]([OH:25])[CH2:22][N:21]3[C:26](=[O:45])[C@@H:27]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[C@H:28]([CH3:36])[CH2:29][CH:30]([CH3:35])[CH2:31][CH2:32]C=C)=[O:19])[CH2:14][C@H:13]2[CH:15]=[CH2:16])=[O:11])(=[O:8])=[O:7])[CH2:5][CH2:4]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>[F:1][CH2:2][C:3]1([S:6]([NH:9][C:10]([C@@:12]23[CH2:14][C@H:13]2[CH:15]=[CH:16][CH2:32][CH2:31][CH:30]([CH3:35])[CH2:29][C@@H:28]([CH3:36])[C@H:27]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:42])([CH3:43])[CH3:41])[C:26](=[O:45])[N:21]2[CH2:22][C@H:23]([OH:25])[CH2:24][C@H:20]2[C:18](=[O:19])[NH:17]3)=[O:11])(=[O:7])=[O:8])[CH2:4][CH2:5]1

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 sparged with nitrogen for 30 min. and then Hoveyda-Grubbs Catalyst 2nd Generation (0.718 g, 1.142 mmol) was added and the reaction 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-f97f133725b2401ea5235d998adad869
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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