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

HRID 522348Notes

Reaction equation

HRID 522348 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-fe54b4e0fa1e416c9a39f8dd8e743455
Source dataset
uspto-grants-2016_05
Patent number
US09328138B2

Reaction notes

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