Trifluoroacetic acid → 1-(3-{[(4-Chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}-4-fluorobenzyl)cyclopropane-carboxylic acid

HRID 1475686Notes

Reaction equation

HRID 1475686 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:30]2[CH2:34][CH2:33][CH2:32][C:31]2([F:36])[F:35])[C:9]([NH:11][C:12]2[CH:13]=[C:14]([CH:26]=[CH:27][C:28]=2[F:29])[CH2:15][C:16]2([C:19]([O:21]C(C)(C)C)=[O:20])[CH2:18][CH2:17]2)=[O:10])=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:30]2[CH2:34][CH2:33][CH2:32][C:31]2([F:36])[F:35])[C:9]([NH:11][C:12]2[CH:13]=[C:14]([CH:26]=[CH:27][C:28]=2[F:29])[CH2:15][C:16]2([C:19]([OH:21])=[O:20])[CH2:17][CH2:18]2)=[O:10])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66563456Tert-butyl 1-(3-{[(4-chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

Product 1

HCID 680069341-(3-{[(4-Chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}-4-fluorobenzyl)cyclopropane-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

750 mg (1.44 mmol) of tert-butyl 1-(3-{[(4-chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate (as racemic diastereomer mixture) were dissolved in 1.6 ml of dichloromethane, and 5.5 ml of TFA were added at RT. The mixture was stirred at RT for 2 h and then concentrated under reduced pressure. The residue was dried under high vacuum and then triturated with acetonitrile. The precipitated solid was filtered off. The filtrate was concentrated, the residue obtained was once more triturated with acetonitrile and a further batch of solid was isolated. This procedure was repeated once more, and all solid batches were then combined. This gave a total of 553 mg (82.6% of theory) of the title compound as a mixture of four isomers.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was dried under high vacuum
  3. customtriturated with acetonitrile
  4. filtrationThe precipitated solid was filtered off
  5. concentrationThe filtrate was concentrated
  6. customthe residue obtained
  7. customwas once more triturated with acetonitrile
  8. customa further batch of solid was isolated

Sources & evidence

ORD record
ord-e68cc310ed69428cbbbeb91ccccc72f7
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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