1,1'-Carbonyldiimidazole → HCID 57945182, compound

HRID 1697888Notes

Reaction equation

HRID 1697888 reaction equation
[C:1]([O:5][C:6]([NH:8][C@:9]1([C:16]([OH:18])=O)[CH2:11][C@H:10]1[CH2:12][CH:13]([F:15])[F:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:31]1([S:34]([NH2:37])(=[O:36])=[O:35])[CH2:33][CH2:32]1.C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O>[CH:31]1([S:34]([NH:37][C:16]([C@@:9]2([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:11][C@H:10]2[CH2:12][CH:13]([F:14])[F:15])=[O:18])(=[O:36])=[O:35])[CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 57945194HCID 57945194, compound

Product 1

HCID 57945182HCID 57945182, compoundYield 76.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1R,2S)-1-(tert-butoxycarbonylamino)-2-(2,2-difluoroethyl)cyclopropanecarboxylic acid (665 mg, 2.507 mmol) in THF (20 mL) was added CDI (528 mg, 3.26 mmol) and the formed solution was stirred at rt for 3 h. Cyclopropanesulfonamide (395 mg, 3.26 mmol) and DBU (0.756 mL, 5.01 mmol) were added and the mixture was stirred at rt overnight. The reaction was diluted with EtOAc and washed with 1.0M HCl solution. The aqueous layer was extracted with EtOAc and the combined organics were washed with 5% citric acid, brine, dried over MgSO4, filtered and evaporated to give crude material. The crude product was purified on the Biotage (acetone/hexanes 5-30%) to give the pure product tert-butyl (1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-(2,2-difluoroethyl)cyclopropylcarbamate (783 mg, 1.913 mmol, 76% yield) as a white solid. 1H NMR (500 MHz, MeOD) δ 1.01-1.15 (m, 2H), 1.16-1.35 (m, 2H), 1.49 (s, 10H), 1.58-1.77 (m, 2H), 1.92-2.19 (m, 2H), 2.90-2.99 (m, 1H), 5.80-6.10 (m, 1H).

Workup

  1. stirringthe mixture was stirred at rt overnight
  2. washwashed with 1.0M HCl solution
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washthe combined organics were washed with 5% citric acid, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give crude material
  9. customThe crude product was purified on the Biotage (acetone/hexanes 5-30%)

Sources & evidence

ORD record
ord-6a7bd2ffac8a4cb5a0bc144c973d25e9
Source dataset
uspto-grants-2012_04
Patent number
US08163921B2

Reaction notes

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