Trifluoroacetic acid → 5-Chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluorobenzoic acid

HRID 1427840Notes

Reaction equation

HRID 1427840 reaction equation
[Cl:1][C:2]1[C:3]([CH2:16][O:17][C:18]2[CH:27]=[C:26]3[C:21]([CH2:22][CH2:23][C:24]([CH3:29])([CH3:28])[O:25]3)=[CH:20][CH:19]=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>C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH2:16][O:17][C:18]2[CH:27]=[C:26]3[C:21]([CH2:22][CH2:23][C:24]([CH3:29])([CH3:28])[O:25]3)=[CH:20][CH:19]=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 86702867Tert-butyl 5-chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluorobenzoate

Product 1

HCID 867028665-Chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluorobenzoic acidYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl 5-chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluorobenzoate (290 mg, 0.689 mmol) and trifluoroacetic acid (10 mL) in DCM (10 mL) was stirred at room temperature for 16 hrs. The solvents were removed and the residue was extracted with EtOAc (150×3 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase combiflash (15%-19% MeCN in 0.5% NH4HCO3) to give target product of 5-chloro-4-((2,2-dimethylchroman-7-yloxy)methyl)-2-fluorobenzoic acid (100 mg, 49%) as a white solid. LCMS (ESI) m/z: 364.9 [M+H].

Workup

  1. customThe solvents were removed
  2. extractionthe residue was extracted with EtOAc (150×3 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase combiflash (15%-19% MeCN in 0.5% NH4HCO3)

Sources & evidence

ORD record
ord-445c60f9735848318ed1d8733cf168d5
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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