4-Fluoroaniline → Ethyl 1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxylate

HRID 1517898Notes

Reaction equation

HRID 1517898 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([C:9]([OH:11])=O)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[F:12][C:13]1[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[F:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:9]([C:6]2([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][CH2:8]2)=[O:11])=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 97314-FluoroanilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 117894721-(Ethoxycarbonyl)cyclopropanecarboxylic acid

Product 1

HCID 56956060Ethyl 1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a mixture of 1-(ethoxycarbonyl)cyclopropanecarboxylic acid (12.9 g, 81.6 mmol), 4-fluorobenzenamine (9.06 g, 81.6 mmol, Alfa-Aesar) and HOAt (2.22 g, 16.3 mmol, Shanghai Medped Co. Ltd.) in DCM (80 mL) was added EDCI (18.76 g, 97.9 mmol, Shanghai Medped Co. Ltd.) in portions at rt. The reaction was warmed up to 45° C. and stirred for 3 h. The mixture was extracted with water (150 mL×5), followed by brine (100 mL). The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was recrystallized in n-hexane to give the title compound as a pale yellow solid (12.83 g, 63%).

Workup

  1. extractionThe mixture was extracted with water (150 mL×5)
  2. dry with materialThe organic phase was dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was recrystallized in n-hexane

Sources & evidence

ORD record
ord-527e652ad29e48b1826cccf9fb4d6b44
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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