Trifluoroacetic acid → [4-(2-{[2-(Methoxycarbonyl)phenyl]thio}ethyl)phenoxy]acetic acid

HRID 898926Notes

Reaction equation

HRID 898926 reaction equation
C([O:5][C:6](=[O:28])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][S:17][C:18]2[CH:27]=[CH:26][CH:25]=[CH:24][C:19]=2[C:20]([O:22][CH3:23])=[O:21])=[CH:11][CH:10]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:23][O:22][C:20]([C:19]1[CH:24]=[CH:25][CH:26]=[CH:27][C:18]=1[S:17][CH2:16][CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:6]([OH:28])=[O:5])=[CH:14][CH:13]=1)=[O:21]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69259277Methyl 2-({2-[4-(2-tert-butoxy-2-oxoethoxy)phenyl]ethyl}thio)benzoate

Product 1

HCID 57640312[4-(2-{[2-(Methoxycarbonyl)phenyl]thio}ethyl)phenoxy]acetic acidYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 2-({2-[4-(2-tert-butoxy-2-oxoethoxy)phenyl]ethyl}thio)benzoate (4.630 g, 11.502 mmol) was take up in DCM (50 ml) and treated with trifluoroacetic acid (44.40 g, 389.405 mmol) at r.t for 4 h. The mixture was evaporated and azeotroped with toluene. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4). The solvent was removed by evaporation to give 3.825 g of [4-(2-{[2-(methoxycarbonyl)phenyl]thio}ethyl)phenoxy]-acetic acid (yield for two steps 63.9% overall).

Workup

  1. customThe mixture was evaporated
  2. customazeotroped with toluene
  3. customThe crude was purified by preparative HPLC (
  4. concentrationthe acetonitrile concentration
  5. temperaturewas increased to 100%
  6. additiona mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min)
  7. additionThe product containing fractions
  8. customthe acetonitrile was removed by evaporation
  9. additionEtOAc (10 ml) was added
  10. washthe organic phase was washed with two portions of brine
  11. dry with materialdried (MgSO4)
  12. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-2b39cf5321224b2084a119740276d4f7
Source dataset
uspto-grants-2008_04
Patent number
US07351858B2

Reaction notes

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