tert-butyl ((2S,3R)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate → tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-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 523172Notes

Reaction equation

HRID 523172 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7](=[O:26])[C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C@H:9]([CH3:17])[CH2:10][CH:11]([CH3:16])[CH2:12][CH2:13][CH:14]=[CH2:15])[C@H:4]([C:27](=[O:44])[NH:28][C@:29]2([C:34](=[O:43])[NH:35][S:36]([C:39]3([CH3:42])[CH2:41][CH2:40]3)(=[O:38])=[O:37])[CH2:31][C@H:30]2C=C)[CH2:3]1>ClCCCl.Cl[Ru](Cl)=CC1C=CC=CC=1OC(C)C>[OH:1][C@H:2]1[CH2:6][N:5]2[C:7](=[O:26])[C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])[C@H:9]([CH3:17])[CH2:10][CH:11]([CH3:16])[CH2:12][CH2:13][CH:14]=[CH:15][C@@H:30]3[CH2:31][C@@:29]3([C:34](=[O:43])[NH:35][S:36]([C:39]3([CH3:42])[CH2:40][CH2:41]3)(=[O:37])=[O:38])[NH:28][C:27](=[O:44])[C@@H:4]2[CH2:3]1

Participants

4

Reactant 1

HCID 86683198tert-butyl ((2S,3R)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate

Product 1

HCID 71004914tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-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)carbamateYield 70%

Reagents, catalysts & solvents 2

HCID 4049424Dichloro(o-isopropoxyphenylmethylene)rutheniumCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of tert-butyl ((2S,3R)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate (8.40 g, 13.2 mmol) in 1,2-dichloroethane (1500 ml) was sparged with nitrogen for 30 min. and then 1,3-Bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium (“Hoveyda-Grubbs Catalyst 2nd Generation”, 0.413 g, 0.657 mmol) was added. The reaction solution was heated to 80° C. for 2 h. The reaction solution was cooled to room temperature and then was concentrated in vacuo. The resulting residue was subjected to silica gel chromatography (hexane:acetone 80:20 to 40:60) to afford tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-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 as a brown solid (5.6 g, 70% yield). MS: MS m/z 611.3 (M++1).

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-97a1e3fa7de84cf69c6302018995d1b6
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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