(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 1666975ノート

反応式

HRID 1666975 の反応式
[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

参加物

5

反応物 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、化合物

生成物 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-carboxylate収率 75.3%

試薬・触媒・溶媒 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)ruthenium触媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-17d05f1f8a1d48f0a6e44f4df98bd2d9
出典データセット
uspto-grants-2011_10
特許番号
US08044087B2

反応ノート

読み込み中…