1,1'-Carbonyldiimidazole → tert-butyl [(1R,2S)-2-ethenyl-1-({[1-(methoxymethyl)cyclopropyl]sulfonyl}carbamoyl)cyclopropyl]carbamate

HRID 522348ノート

反応式

HRID 522348 の反応式
[C:1]([O:5][C:6]([NH:8][C@:9]1([C:14]([OH:16])=O)[CH2:11][C@H:10]1[CH:12]=[CH2:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:29][O:30][CH2:31][C:32]1([S:35]([NH2:38])(=[O:37])=[O:36])[CH2:34][CH2:33]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[CH:12]([C@@H:10]1[CH2:11][C@:9]1([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:14](=[O:16])[NH:38][S:35]([C:32]1([CH2:31][O:30][CH3:29])[CH2:34][CH2:33]1)(=[O:37])=[O:36])=[CH2:13]

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10376443(1R,2S)-1-(((1,1-Dimethylethoxy)carbonyl)amino)-2-ethenylcyclopropanecarboxylic acidHCID 224992771-(Methoxymethyl)cyclopropane-1-sulfonamide

生成物 1

HCID 131735528tert-butyl [(1R,2S)-2-ethenyl-1-({[1-(methoxymethyl)cyclopropyl]sulfonyl}carbamoyl)cyclopropyl]carbamate収率 55.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of (1R,2S)-1-[(tert-butoxycarbonyl)amino]-2-ethenylcyclopropanecarboxylic acid (132 mg) in THF (3 mL) was added 1,1′-carbonyldiimidazole (283 mg). The mixture was stirred 4 hours at reflux. The mixture was cooled to room temperature and a solution of 1-(methoxymethyl)cyclopropanesulfonamide (125 mg; Li et al., 2006, Synlett 5:725) and DBU (0.438 mL) in THF (3 mL) was added via cannula. The mixture was stirred for 40 hours at room temperature. The reaction was quenched with 1N HCl and the mixture was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (ISCO) to give the desired product (120 mg). 1H NMR (400 MHz, CDCl3): 5.71-5.62 (m, 1H), 5.29 (d, 1H), 5.16 (d, 1H), 3.36 (s, 2H), 2.15 (dt, 1H), 1.89 (dd, 1H), 1.75-1.68 (m, 2H), 1.49 (s, 9H), 1.34-1.30 (m, 1H), 1.08-1.03 (m, 2H).

後処理

  1. temperatureat reflux
  2. stirringThe mixture was stirred for 40 hours at room temperature
  3. customThe reaction was quenched with 1N HCl
  4. extractionthe mixture was extracted twice with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by flash chromatography (ISCO)

出典と根拠

ORDレコード
ord-fe54b4e0fa1e416c9a39f8dd8e743455
出典データセット
uspto-grants-2016_05
特許番号
US09328138B2

反応ノート

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