1,4-Cyclohexadiene → N-(4-Fluorophenyl)-N'-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide

HRID 445478Notes

Reaction equation

HRID 445478 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23]CC4C=CC=CC=4)=[CH:19][CH:18]=3)=[O:15])[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.C1CC=CCC=1>CCO.[Pd]>[OH:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:14]([C:11]2([C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[O:10])[CH2:13][CH2:12]2)=[O:15])=[CH:18][CH:19]=1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 57810288Cyclopropane-1,1-dicarboxylic acid (4-benzyloxy-phenyl)-amide (4-fluoro-phenyl)-amide

Product 1

HCID 57810197N-(4-Fluorophenyl)-N'-(4-hydroxyphenyl)cyclopropane-1,1-dicarboxamideYield 96.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a refluxing mixture of cyclopropane-1,1-dicarboxylic acid (4-benzyloxy-phenyl)-amide (4-fluoro-phenyl)-amide (46 g, 113 mmol), 10% Pd/C (2 g) in EtOH (400 mL) was added dropwise 1,4-cyclohexadiene (62.7 mL, 678 mmol). Stirring was continued for 2-5 h until the reaction was complete. The mixture was cooled to rt, filtered through celite, and washed with EtOH. The solution was then concentrated under reduced pressure. To the flask containing the crude product was added CHCl3 (200 mL). The resulting suspension was stirred for 15 min at rt. The solid was filtered, and dried in the air to give cyclopropane-1,1-dicarboxylic acid (4-fluoro-phenyl)-amide(4-hydroxy-phenyl)-amide (34.4 g, 95%, yield).

Workup

  1. filtrationfiltered through celite
  2. washwashed with EtOH
  3. concentrationThe solution was then concentrated under reduced pressure
  4. additionTo the flask containing the crude product
  5. additionwas added CHCl3 (200 mL)
  6. stirringThe resulting suspension was stirred for 15 min at rt
  7. filtrationThe solid was filtered
  8. customdried in the air

Sources & evidence

ORD record
ord-85f26bebf3224db58debca73eec7d0ae
Source dataset
uspto-grants-2013_07
Patent number
US08476298B2

Reaction notes

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