Hydrochloric Acid → HCID 67155119, compound

HRID 1915961Notes

Reaction equation

HRID 1915961 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:12]([OH:14])=O)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC1C(O)=C(F)C(F)=C(F)C=1F.CCN=C=NCCCN(C)C.Cl.[Li+].CC([N-]C(C)C)C.[CH3:47][O:48][C:49](=[O:51])[CH3:50]>C(Cl)Cl.CN(C1C=CN=CC=1)C.C1COCC1>[CH3:47][O:48][C:49](=[O:51])[CH2:50][C:12]([C:9]1([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:10][CH2:11]1)=[O:14]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 6584Methyl AcetateHCID 13041PentafluorophenolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 6883961-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acid2×HCID 2724682Lithium diisopropylamide

Product 1

HCID 67155119HCID 67155119, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 1-tert-Butoxycarbonylamino-cyclopropanecarboxylic acid 1 (2.077 g, 10.3 mmol) in CH2Cl2 (44 mL) was added DMAP (258 mg, 2.11 mmol), pentafluorophenol (2.100 g, 11.4 mmol) and EDAC (2.369 g, 12.3 mmol) and the reaction mixture was stirred at rt for 1 h 50 min. 1M HCl (aq) (40 mL) was added, the layers were separated and, after washing with saturated NaHCO3 (aq) (40 mL) and then with saturated brine (40 mL), the organic layer was dried (MgSO4), concentrated in vacuo, and placed under high vacuum. To THF (12.5 mL) at −78° C. was added LDA (2.0 M, 17 mL, 34 mmol) followed by methylacetate (2.6 mL, 32.7 mmol) in dropwise fashion. The reaction was stirred for 30 min, and the intermediate ester of 1-tert-butoxycarbonylamino-cyclopropanecarboxylic acid was added in THF (35 mL), and the resulting mixture was stirred for 3 h 20 min. The mixture was quenched with 1M HCl (aq) (50 mL), the layers were separated and washed with saturated NaHCO3 (aq) (50 mL) and brine (50 mL). Following extraction with EtOAc, the combined organics were dried (MgSO4) and concentrated in vacuo. Purification was carried out by flash column chromatography on silica (eluant 3:7-4:6-1:1 EtOAc/Hexane) to give 2 (1.0526 g, 4.09 mmol, 40%) as a yellow oil.

Workup

  1. customthe layers were separated
  2. washafter washing with saturated NaHCO3 (aq) (40 mL)
  3. dry with materialwith saturated brine (40 mL), the organic layer was dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. stirringThe reaction was stirred for 30 min
  6. stirringthe resulting mixture was stirred for 3 h 20 min
  7. customThe mixture was quenched with 1M HCl (aq) (50 mL)
  8. customthe layers were separated
  9. washwashed with saturated NaHCO3 (aq) (50 mL) and brine (50 mL)
  10. extractionextraction with EtOAc
  11. dry with materialthe combined organics were dried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customPurification

Sources & evidence

ORD record
ord-f8e6947dbd3d489ca057000eda41a094
Source dataset
uspto-grants-2013_12
Patent number
US08614193B2

Reaction notes

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