Trifluoroacetic acid → 4-[(1S)-1-({[5-Chloro-2-(4-fluorophenoxy)pyridin-3-YL]carbonyl}amino)ethyl]benzoic acid

HRID 1293182Notes

Reaction equation

HRID 1293182 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([C:23]([NH:25][C@H:26]([C:28]2[CH:40]=[CH:39][C:31]([C:32]([O:34]C(C)(C)C)=[O:33])=[CH:30][CH:29]=2)[CH3:27])=[O:24])[C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:13][CH:14]=1>ClCCl>[Cl:8][C:9]1[CH:10]=[C:11]([C:23]([NH:25][C@H:26]([C:28]2[CH:29]=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:39][CH:40]=2)[CH3:27])=[O:24])[C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:13][CH:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69050742tert-butyl 4-[(1S)-1-({[5-Chloro-2-(4-fluorophenoxy)pyridin-3-yl]carbonyl}amino)ethyl]benzoate

Product 1

HCID 116830884-[(1S)-1-({[5-Chloro-2-(4-fluorophenoxy)pyridin-3-YL]carbonyl}amino)ethyl]benzoic acidYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (10 mL) was added to a solution of tert-butyl 4-[(1S)-1-({[5-Chloro-2-(4-fluorophenoxy)pyridin-3-yl]carbonyl}amino)ethyl]benzoate (step 4, 2.1 g; 4.3 mmol) in dichloromethane (30 mL). The reaction mixture was stirred at room temperature until the starting material was fully consumed (4 h). The solvent and most of the trifluoroacetic acid were removed under reduced pressure. The residue was purified by flush silica gel column chromatography on silica gel (50 g) eluting with dichloromethane/methanol (20/1) and recrystallization (ethyl acetate-diisopropyl ether) to give 1.24 g, (86%) of the title compounds as white crystals: mp 198.2° C.;

Workup

  1. customwas fully consumed (4 h)
  2. customThe solvent and most of the trifluoroacetic acid were removed under reduced pressure
  3. customThe residue was purified
  4. customby flush silica gel column chromatography on silica gel (50 g)
  5. washeluting with dichloromethane/methanol (20/1) and recrystallization (ethyl acetate-diisopropyl ether)

Sources & evidence

ORD record
ord-3ffa0587373041ac814809117247c12c
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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