Triethylamine → 1-(4-Bromo-2-fluorophenyl)cyclopropanecarbohydrazide

HRID 1423998Notes

Reaction equation

HRID 1423998 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11](O)=[O:12])[CH2:10][CH2:9]2)=[C:4]([F:14])[CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.O.O[N:29]1C2C=CC=CC=2N=[N:30]1.C(N(CC)CC)C>CN(C)C=O.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([NH:29][NH2:30])=[O:12])[CH2:10][CH2:9]2)=[C:4]([F:14])[CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 666626821-(4-Bromo-2-fluorophenyl)cyclopropane-1-carboxylic acid

Product 1

HCID 867128521-(4-Bromo-2-fluorophenyl)cyclopropanecarbohydrazideYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of the compound (26.55 g, 102.5 mmol) obtained in Example 14-3), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (21.6 g, 112.7 mmol), 1-hydroxybenzotriazole monohydrate (17.26 g, 112.7 mmol), triethylamine (42.9 mL, 307 mmol), and tert-butoxycarbonylhydrazide (16.3 g, 123 mmol) in N,N-dimethylformamide (400 mL) was stirred overnight at room temperature. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated sodium chloride solution and then dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. A 4 M solution (60 mL) of hydrochloric acid in 1,4-dioxane and methanol (300 mL) were added to the obtained partially purified product, and the mixture was stirred at room temperature for 6.5 h. The reaction mixture was concentrated under reduced pressure, dichloromethane was added to the residue, and the organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated sodium chloride solution and then dried with anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure, hexane was added to the obtained partially purified product, and the solid was collected by filtration to obtain the title compound (11.6 g, 42%) as a colorless solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated sodium chloride solution
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additionA 4 M solution (60 mL) of hydrochloric acid in 1,4-dioxane and methanol (300 mL) were added to the
  7. customobtained partially purified product
  8. concentrationThe reaction mixture was concentrated under reduced pressure, dichloromethane
  9. additionwas added to the residue
  10. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated sodium chloride solution
  11. dry with materialdried with anhydrous sodium sulfate
  12. concentrationThe filtrate was concentrated under reduced pressure, hexane
  13. additionwas added to the
  14. customobtained partially purified product
  15. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-6b821055acf74105afb3466947dfd263
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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