Trifluoroacetic acid → 1-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}benzyl)-2,2-difluorocyclopropanecarboxylic acid

HRID 1475687Notes

Reaction equation

HRID 1475687 reaction equation
[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][C:7]2([C:12]([O:14]C(C)(C)C)=[O:13])[CH2:9][C:8]2([F:11])[F:10])=[CH:4][C:3]=1[NH:21][C:22](=[O:37])[C@H:23]([C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)[C@@H:24]([CH3:29])[C:25]([F:28])([F:27])[F:26].C(O)(C(F)(F)F)=O>ClCCl>[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][C:7]2([C:12]([OH:14])=[O:13])[CH2:9][C:8]2([F:11])[F:10])=[CH:4][C:3]=1[NH:21][C:22](=[O:37])[C@H:23]([C:30]1[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=1)[C@@H:24]([CH3:29])[C:25]([F:26])([F:27])[F:28]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86667526tert-butyl 1-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}benzyl)-2,2-difluorocyclopropanecarboxylate

Product 1

HCID 573444411-(4-Chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}benzyl)-2,2-difluorocyclopropanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1.80 g (3.18 mmol) of tert-butyl 1-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}benzyl)-2,2-difluorocyclopropanecarboxylate (as diastereomer mixture) were dissolved in 5 ml of dichloromethane, and 4.9 ml of TFA were added at RT. The reaction mixture was stirred at RT for 1 h and then concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase first dichloromethane, then dichloromethane/ethyl acetate 10:1→5:1). This gave 1.25 g of the target compound (77.1% of theory).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by chromatography on silica gel (mobile phase first dichloromethane

Sources & evidence

ORD record
ord-89057cb0080846d2aabc686894fac584
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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