Trifluoroacetic acid → 5-Chloro-4-(6-cyclopropyl-5-(1,1-difluoroethoxy)pyridin-3-yloxy)-2-fluorobenzoic acid

HRID 2048120Notes

Reaction equation

HRID 2048120 reaction equation
[Cl:1][C:2]1[C:3]([O:16][C:17]2[CH:18]=[N:19][C:20]([CH:28]3[CH2:30][CH2:29]3)=[C:21]([O:23][C:24]([F:27])([F:26])[CH3:25])[CH:22]=2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([O:9]C(C)(C)C)=[O:8].FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[C:3]([O:16][C:17]2[CH:18]=[N:19][C:20]([CH:28]3[CH2:30][CH2:29]3)=[C:21]([O:23][C:24]([F:27])([F:26])[CH3:25])[CH:22]=2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([OH:9])=[O:8]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58042461HCID 58042461, compound

Product 1

HCID 580424975-Chloro-4-(6-cyclopropyl-5-(1,1-difluoroethoxy)pyridin-3-yloxy)-2-fluorobenzoic acidYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 5-chloro-4-(6-cyclopropyl-5-(1,1-difluoroethoxy)pyridin-3-yloxy)-2-fluorobenzoate (Preparation 270, 260 mg, 0.59 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (440 μL, 5.86 mmol). The reaction mixture was stirred over 48 hours at room temperature then concentrated in vacuo and the crude residue azeotroped with methanol (2×25 mL). The crude material was purified by silica gel column chromatography eluting with 50% ethyl acetate in heptane to afford the title compound as a white solid (200 mg, 96%).

Workup

  1. concentrationthen concentrated in vacuo
  2. customthe crude residue azeotroped with methanol (2×25 mL)
  3. customThe crude material was purified by silica gel column chromatography
  4. washeluting with 50% ethyl acetate in heptane

Sources & evidence

ORD record
ord-38004ac2ae8842f6a8e06be43ed147ec
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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