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

HRID 1443433Notes

Reaction equation

HRID 1443433 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.Cl.[CH2:13]([O:15][C:16]([C:18]1([NH2:23])[CH2:20][CH:19]1[CH:21]=[CH2:22])=[O:17])[CH3:14].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>[CH2:13]([O:15][C:16]([C:18]1([NH:23][C:9]([CH:6]2[CH2:5][CH:4]3[CH2:8][CH:7]2[C:2](=[O:1])[O:3]3)=[O:11])[CH2:20][CH:19]1[CH:21]=[CH2:22])=[O:17])[CH3:14]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 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%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 13 (857 mg, 5.5 mmol), in DMF (14 mL) and DCM (25 mL) at room temperature, was added the hydrochloride of 1-amino-2-vinyl-cyclopropanecarboxylic acid ethyl ester, prepared as described in WO03/099274, (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 redissolved in DCM (100 mL) and 0.1 M HCl (aq) and the phases were separated. The organic phase was washed with NaHCO3 (aq) and brine, dried (MgSO4) and filtered. Removal of the solvent in vacuo afforded the target compound (1.6 g, 99%). LC/MS>95%, m/z (ESI+)=294 (MH+)

Workup

  1. customprepared
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was redissolved in DCM (100 mL)
  4. custom0.1 M HCl (aq) and the phases were separated
  5. washThe organic phase was washed with NaHCO3 (aq) and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-b131091ad7cd4a5e8e94979e4e0b50d1
Source dataset
uspto-grants-2010_02
Patent number
US07659245B2

Reaction notes

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