Potassium Hydroxide → 2-[(4-{3-[Ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoic acid

HRID 899903Notes

Reaction equation

HRID 899903 reaction equation
[CH2:1]([N:3]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[F:33])[C:4](=[O:25])[CH2:5][CH2:6][C:7]1[CH:24]=[CH:23][C:10]([O:11][CH2:12][C:13]2[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=2[C:15]([O:17]C)=[O:16])=[CH:9][CH:8]=1)[CH3:2].[OH-].[K+]>CCO>[CH2:1]([N:3]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[F:33])[C:4](=[O:25])[CH2:5][CH2:6][C:7]1[CH:24]=[CH:23][C:10]([O:11][CH2:12][C:13]2[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=2[C:15]([OH:17])=[O:16])=[CH:9][CH:8]=1)[CH3:2]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 69120429Methyl 2-[(4-{3-[ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]-benzoate

Product 1

HCID 104107172-[(4-{3-[Ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoic acidYield 18.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl 2-[(4-{3-[ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]-benzoate (0.454 g, 1.001 mmol) was dissolved in EtOH (5 ml) and potassium hydroxide (0.085 g, 1.514 mmol) was added. The reaction was performed in a single node microwave oven (7 min, 150° C.). Workup was by removing the solvent by evaporation, addition of HCl (20 ml, 1 M) and the water phase was washed with two portions of EtOAc (20 ml). The organic phases were pooled and the solvent was removed by evaporation. The crude was purified by preparative HPLC (starting 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 0.079 g of 2-[(4-{3-[ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoic acid (18.0%).

Workup

  1. customThe reaction was performed in a single node microwave oven
  2. custom(7 min, 150° C.)
  3. customby removing the solvent
  4. customby evaporation, addition of HCl (20 ml, 1 M)
  5. washthe water phase was washed with two portions of EtOAc (20 ml)
  6. customthe solvent was removed by evaporation
  7. customThe crude was purified by preparative HPLC (
  8. concentrationthe acetonitrile concentration
  9. temperaturewas increased to 100%
  10. 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)
  11. customthe acetonitrile was removed by evaporation
  12. additionEtOAc (10 ml) was added
  13. washthe organic phase was washed with two portions of brine
  14. dry with materialdried (MgSO4)
  15. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-52d6b523ce49468cb376d3a18dbb4056
Source dataset
uspto-grants-2008_04
Patent number
US07355069B2

Reaction notes

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