Hydrochloric Acid → HCID 89853996, compound

HRID 931067Notes

Reaction equation

HRID 931067 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:7]2([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[CH2:9][CH2:8]2)[CH:6]=1.[K+].[CH:21]1([B-](F)(F)F)[CH2:23][CH2:22]1.ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>[Cl-].[Na+].O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(OCC)(=O)C>[CH:21]1([C:2]2[CH:3]=[N:4][N:5]([C:7]3([C:10]([O:12][CH2:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)=[O:11])[CH2:9][CH2:8]3)[CH:6]=2)[CH2:23][CH2:22]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 23697338Potassium cyclopropyltrifluoroborateHCID 117966282HCID 117966282, compound

Product 1

HCID 89853996HCID 89853996, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

Into a 20 mL microwave vial were added benzyl 1-(4-bromo-1H-pyrazol-1-yl)cyclopropanecarboxylate (421 mg, 1.31 mmol), cyclopropyltrifluoroborate potassium salt (582 mg, 3.93 mmol), 1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (42.5 mg, 0.052 mmol) and cesium carbonate (1710 mg, 5.24 mmol). The vial was sealed, evacuated and backflushed with nitrogen two times followed by the addition of tetrahydrofuran (7 mL). The reaction mixture was stirred at 80° C. for 18 h. The solvent was removed under reduced pressure and to the residue was added water (100 mL) and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×). After the second extraction an emulsion formed that was cleared with the addition of brine, ethyl acetate and aqueous hydrochloric acid (1N). The aqueous layers were extracted again with ethyl acetate (2×), the solvent was removed under reduced pressure and the residue was purified via flash chromatography (0-100% ethyl acetate in heptanes) to afford benzyl 1-(4-cyclopropyl-1H-pyrazol-1-yl)cyclopropanecarboxylate (91 mg, 25%). MS (ES+) (M+H) 283.3; LCMS retention time: 3.38 minutes (Method L).

Workup

  1. customThe vial was sealed
  2. customevacuated
  3. additionfollowed by the addition of tetrahydrofuran (7 mL)
  4. customThe solvent was removed under reduced pressure and to the residue
  5. additionwas added water (100 mL) and ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (2×)
  8. extractionAfter the second extraction an emulsion
  9. customformed
  10. extractionThe aqueous layers were extracted again with ethyl acetate (2×)
  11. customthe solvent was removed under reduced pressure
  12. customthe residue was purified via flash chromatography (0-100% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-078c77b1c3bc4659834f443446564d42
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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