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 1481654Notes

Reaction equation

HRID 1481654 reaction equation
[C:1]([O:5][C:6](=[O:44])[NH:7][C@@H:8]([C@H:35]([CH3:43])[CH2:36][CH:37]([CH3:42])[CH2:38][CH2:39][CH:40]=C)[C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[C:17](=[O:34])[NH:18][C@:19]1([C:24](=[O:33])[NH:25][S:26]([C:29]2([CH3:32])[CH2:31][CH2:30]2)(=[O:28])=[O:27])[CH2:21][C@H:20]1[CH:22]=C)=[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:44])[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:34])[NH:18][C@:19]2([C:24](=[O:33])[NH:25][S:26]([C:29]3([CH3:32])[CH2:30][CH2:31]3)(=[O:27])=[O:28])[CH2:21][C@H:20]2[CH:22]=[CH:40][CH2:39][CH2:38][CH:37]([CH3:42])[CH2:36][C@H:35]1[CH3:43])([CH3:4])([CH3:3])[CH3:2]

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 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalyst2×HCID 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 (8.4 g, 13.15 mmol) in DCE (1500 ml) was degassed 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 concentrated in vacuo the and resulting residue was purified by silica gel chromatography using a gradient of 20-60% Acetone in hexanes to give the mixture of diastereomers 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. concentrationThe reaction solution was concentrated in vacuo the and
  2. customresulting residue
  3. customwas purified by silica gel chromatography
  4. customto give

Sources & evidence

ORD record
ord-d5712ef8702944bda504687e7de58f78
Source dataset
uspto-grants-2016_08
Patent number
US09409943B2

Reaction notes

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