1,1'-Carbonyldiimidazole → Tert-butyl 1-(cyclopropylsulfonylcarbamoyl)-2-(difluoromethyl)cyclopropylcarbamate

HRID 1365014Notes

Reaction equation

HRID 1365014 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:15]([OH:17])=O)[CH2:11][CH:10]1[CH:12]([F:14])[F:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:30]1([S:33]([NH2:36])(=[O:35])=[O:34])[CH2:32][CH2:31]1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH:30]1([S:33]([NH:36][C:15]([C:9]2([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:11][CH:10]2[CH:12]([F:13])[F:14])=[O:17])(=[O:35])=[O:34])[CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 579450431-(Tert-butoxycarbonylamino)-2-(difluoromethyl)cyclopropanecarboxylic acid

Product 1

HCID 57945025Tert-butyl 1-(cyclopropylsulfonylcarbamoyl)-2-(difluoromethyl)cyclopropylcarbamateYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-(tert-butoxycarbonylamino)-2-(difluoromethyl)cyclopropanecarboxylic acid (975 mg, 3.88 mmol) and CDI (755 mg, 4.66 mmol) in tetrahydrofuran (10 mL) was heated at reflux for 1 h. It was then cooled to rt and then cyclopropanesulfonamide (564 mg, 4.66 mmol) was added, followed by DBU (0.702 mL, 4.66 mmol). This mixture was stirred at rt for 18 h. It was then concentrated in vacuo, diluted with water and adjusted to pH=4 using 1 N HCl. The acidic solution was extracted with EtOAc, washed with water (5×15 mL), dried (MgSO4), and concentrated in vacuo to yield 1.6 g of the crude product as a white solid. Recrystallization from hexane/EtOAc gave 1.15 g (84%) of tert-butyl 1-(cyclopropylsulfonylcarbamoyl)-2-(difluoromethyl)cyclopropylcarbamate as a white solid. LC-MS, MS m/z 377 (M+1+Na).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. concentrationIt was then concentrated in vacuo
  4. additiondiluted with water
  5. extractionThe acidic solution was extracted with EtOAc
  6. washwashed with water (5×15 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto yield 1.6 g of the crude product as a white solid
  10. customRecrystallization from hexane/EtOAc

Sources & evidence

ORD record
ord-bc329fc959004a65ba88a58edb031c23
Source dataset
uspto-grants-2011_02
Patent number
US07888464B2

Reaction notes

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