Diisopropylethylamine → 1-[(3-Oxo-2-oxa-bicyclo[2.2.1]heptane-5-carbonyl)-amino]-2-vinyl-cyclo-propane carboxylic acid ethyl ester

HRID 390112Notes

Reaction equation

HRID 390112 reaction equation
[O:1]=[C:2]1[CH:7]2[CH2:8][CH:4]([CH2:5][CH:6]2[C:9]([OH:11])=O)[O:3]1.[CH2:12]([O:14][C:15]([C:17]1([NH2:22])[CH2:19][CH:18]1[CH:20]=[CH2:21])=[O:16])[CH3:13].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[CH2:12]([O:14][C:15]([C:17]1([NH:22][C:9]([CH:6]2[CH2:5][CH:4]3[CH2:8][CH:7]2[C:2](=[O:1])[O:3]3)=[O:11])[CH2:19][CH:18]1[CH:20]=[CH2:21])=[O:16])[CH3:13]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22082824Ethyl 1-amino-2-vinylcyclopropanecarboxylateHCID 462449653-Oxo-2-oxabicyclo[2.2.1]heptane-5-carboxylic acid

Product 1

HCID 668704341-[(3-Oxo-2-oxa-bicyclo[2.2.1]heptane-5-carbonyl)-amino]-2-vinyl-cyclo-propane carboxylic acid ethyl esterYield 99.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-oxo-2-oxa-bicyclo[2.2.1]heptane-5-carboxylic acid (857 mg, 5.5 mmol), in DMF (14 ml) and DCM (25 ml) at room temperature, was added 1-amino-2-vinylcyclopropanecarboxylic acid ethyl ester (1.15 g, 6.0 mmol), HATU (2.29 g, 6.0 mmol) and DIPEA (3.82 ml, 22 mmol). The reaction was stirred under N2-atmosphere at ambient temperature for 1 h. LC/MS analysis showed complete conversion and the reaction mixture was concentrated in vacuo. The residue was re-dissolved in DCM (100 ml) and 0.1 M HCl (aq) and the layers separated. The organic phase was washed with NaHCO3 (aq) and brine, dried (MgSO4) and filtered. Removal of the solvent in vacuo afforded the title compound (1.6 g, 99%). LC/MS (Method A): tR=2.46 min, >95%, m/z (ESI+)=294(MH+)

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was re-dissolved in DCM (100 ml)
  3. custom0.1 M HCl (aq) and the layers separated
  4. washThe organic phase was washed with NaHCO3 (aq) and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-57689a36e03349d38db96e39d0d76196
Source dataset
uspto-grants-2013_02
Patent number
US08383584B2

Reaction notes

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