(2S,4R)-methyl 4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)dec-9-enoyl)pyrrolidine-2-carboxylate → (3S,14R,16S,E)-methyl 14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadec-10-ene-16-carboxylate

HRID 1666975Notes

Reaction equation

HRID 1666975 reaction equation
[CH2:1]([S:4][C@:5]1([C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[CH:35][CH:34]=2)[CH2:9][N:8]([C:10](=[O:28])[C@@H:11]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]C=C)[C@H:7]([C:29]([O:31][CH3:32])=[O:30])[CH2:6]1)[CH:2]=[CH2:3].SC1N=CC=CC=1C(O)=O>ClCCl.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:36]1([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:35]=[CH:34][C:33]([C@@:5]23[CH2:9][N:8]([C@H:7]([C:29]([O:31][CH3:32])=[O:30])[CH2:6]2)[C:10](=[O:28])[C@@H:11]([NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:3]=[CH:2][CH2:1][S:4]3)=[CH:38][CH:37]=1

Participants

5

Reactant 2

HCID 67443577(2S,4R)-methyl 4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)dec-9-enoyl)pyrrolidine-2-carboxylateHCID 178524460HCID 178524460, compound

Product 1

HCID 67443818(3S,14R,16S,E)-methyl 14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadec-10-ene-16-carboxylateYield 75.3%

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 6344DichloromethaneSolvent

Procedure

A solution of (2S,4R)-methyl 4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)dec-9-enoyl)pyrrolidine-2-carboxylate (108 mg, 0.174 mmol) in Dichloromethane (50 mL) was purged with nitrogen for 30 min. And then Hoveyda-Grubbs Catalyst 2nd Generation (131 mg, 0.209 mmol) was added. The resulting green solution was heated to reflux for 5 h. The reaction was quenched with 2-Mercaptonicotinic acid (54.0 mg, 0.348 mmol) and washed with sat. Na2CO3, and brine. Dried over MgSO4, filtered, concentrated in vacuo. The brown residue was purified by Biotage column, eluted with gradient 5%˜40% EtOAc-Hexane to afford the desired product (3S,14R,16S,E)-methyl 14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2.1]heptadec-10-ene-16-carboxylate (86 mg, 0.131 mmol, 75% yield) as an off-white solid.

Workup

  1. temperatureThe resulting green solution was heated
  2. temperatureto reflux for 5 h
  3. washwashed with sat. Na2CO3, and brine
  4. dry with materialDried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe brown residue was purified by Biotage column
  8. washeluted with gradient 5%˜40% EtOAc-Hexane

Sources & evidence

ORD record
ord-17d05f1f8a1d48f0a6e44f4df98bd2d9
Source dataset
uspto-grants-2011_10
Patent number
US08044087B2

Reaction notes

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