1,8-Diazabicyclo(5.4.0)undec-7-ene → tert-butyl (1R,2R)-2-(difluoromethyl)-1-(1-(hept-6-enyl)cyclopropylsulfonylcarbamoyl)cyclopropylcarbamate

HRID 2061421Notes

Reaction equation

HRID 2061421 reaction equation
[C:1]([O:5][C:6]([NH:8][C@:9]1([C:15]([OH:17])=O)[CH2:11][C@H:10]1[CH:12]([F:14])[F:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:18]([C:25]1([S:28]([NH2:31])(=[O:30])=[O:29])[CH2:27][CH2:26]1)[CH2:19][CH2:20][CH2:21][CH2:22][CH:23]=[CH2:24].C1CCN2C(=NCCC2)CC1>O1CCCC1.CCOC(C)=O>[F:14][CH:12]([F:13])[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:15](=[O:17])[NH:31][S:28]([C:25]1([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH:23]=[CH2:24])[CH2:27][CH2:26]1)(=[O:29])=[O:30]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 57816887(1R,2R)-1-((tert-Butoxycarbonyl)amino)-2-(difluoromethyl)cyclopropanecarboxylic acidHCID 593662391-(Hept-6-enyl)cyclopropane-1-sulfonamide

Product 1

HCID 59366236tert-butyl (1R,2R)-2-(difluoromethyl)-1-(1-(hept-6-enyl)cyclopropylsulfonylcarbamoyl)cyclopropylcarbamateYield 25.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1R,2R)-1-(tert-butoxycarbonylamino)-2-(difluoromethyl)cyclopropanecarboxylic acid (100 mg, 0.398 mmol) in Tetrahydrofuran (4 mL) was added CDT (84 mg, 0.517 mmol) and the formed solution was stirred at r.t. for 3 h. 1-(hept-6-enyl)cyclopropane-1-sulfonamide (104 mg, 0.478 mmol) and DBU (0.120 mL, 0.796 mmol) were added and the reaction continued at r.t. overnight. The reaction was diluted with EtOAc. Washed with 5% citric acid, brine, dried over MgSO4, filtered and concentrated. The residue was purified by Biotage column, eluted with gradient 5%˜70% EtOAc-Hexane to afford the desire produce tert-butyl (1R,2R)-2-(difluoromethyl)-1-(1-(hept-6-enyl)cyclopropylsulfonylcarbamoyl)cyclopropylcarbamate (45 mg, 0.100 mmol, 25.09% yield). 1H NMR (400 MHz, CHLOROFORM-D) ppm 0.95 (s, 2 H) 1.28-1.36 (m, 2 H) 1.36-1.47 (m, 6 H) 1.52 (s, 9 H) 1.58-1.67 (m, 2 H) 1.72 (d, J=10.54 Hz, 1 H) 1.78-1.95 (m, 2 H) 1.97-2.12 (m, 3 H) 4.88-5.05 (m, 2 H) 5.23 (b, NH) 5.65-5.92 (m, 2 H) 9.20 (b, NH).

Workup

  1. waitthe reaction continued at r.t. overnight
  2. washWashed with 5% citric acid, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by Biotage column
  7. washeluted with gradient 5%˜70% EtOAc-Hexane
  8. customto afford the desire

Sources & evidence

ORD record
ord-66e9988db1294ebaa7bbd1c809f90984
Source dataset
uspto-grants-2012_10
Patent number
US08283310B2

Reaction notes

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