1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Cyclopropane-1,1-dicarboxylic acid (4-benzyloxy-phenyl)-amide (4-fluoro-phenyl)-amide

HRID 1924158Notes

Reaction equation

HRID 1924158 reaction equation
Cl.[CH2:2]([O:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]2([C:30](O)=[O:31])[CH2:29][CH2:28]2)=[O:26])=[CH:20][CH:19]=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[F:17][C:18]1[CH:19]=[CH:20][C:21]([NH:24][C:25]([C:27]2([C:30]([NH:14][C:13]3[CH:12]=[CH:11][C:10]([O:9][CH2:2][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)=[CH:16][CH:15]=3)=[O:31])[CH2:29][CH2:28]2)=[O:26])=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27238314-Benzyloxyaniline hydrochlorideHCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic Acid

Product 1

HCID 57810288Cyclopropane-1,1-dicarboxylic acid (4-benzyloxy-phenyl)-amide (4-fluoro-phenyl)-amideYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 0° C. suspension of 4-benzyloxyaniline hydrochloride (47.0 g, 200 mmol) and 1-(4-fluoro-phenylcarbamoyl)-cyclopropanecarboxylic acid (49.1 g, 220 mmol) in CH2Cl2 (400 mL) was added EDCI (38.2 g, 200 mmol). Stirring was continued at rt for 2-4 h until the reaction was complete. CH2Cl2 was removed under reduced pressure. H2O (300 mL) and MeOH (200 mL) were added, and the resulting mixture was stirred at rt for 30 min. After filtration and wash with H2O, the solid was transferred to another flask containing 300 mL of sat. aqueous NaHCO3 solution. The mixture was stirred for another 30 min. The solid was filtered, washed with water, and dried over night on a lyophilizer, affording cyclopropane-1,1-dicarboxylic acid (4-benzyloxy-phenyl)-amide (4-fluoro-phenyl)-amide (75.8 g, 95% yield) as an off-white solid.

Workup

  1. customCH2Cl2 was removed under reduced pressure
  2. additionH2O (300 mL) and MeOH (200 mL) were added
  3. stirringthe resulting mixture was stirred at rt for 30 min
  4. filtrationAfter filtration
  5. washwash with H2O
  6. customthe solid was transferred to another flask
  7. additioncontaining 300 mL of sat. aqueous NaHCO3 solution
  8. stirringThe mixture was stirred for another 30 min
  9. filtrationThe solid was filtered
  10. washwashed with water
  11. customdried over night on a lyophilizer

Sources & evidence

ORD record
ord-da624cb2781840fa84974b81bf28ac97
Source dataset
uspto-grants-2012_05
Patent number
US08178532B2

Reaction notes

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