Hydrochloric Acid → HCID 10411648, compound

HRID 2112007Notes

Reaction equation

HRID 2112007 reaction equation
[CH2:1]([O:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][CH2:15][C:16]2[CH:17]=[C:18]([CH:31]=[CH:32][CH:33]=2)[O:19][CH2:20][C:21]2[CH:30]=[CH:29][CH:28]=[CH:27][C:22]=2[C:23]([O:25]C)=[O:24])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].Cl>C1COCC1.O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:13][CH2:14][CH2:15][C:16]2[CH:17]=[C:18]([CH:31]=[CH:32][CH:33]=2)[O:19][CH2:20][C:21]2[CH:30]=[CH:29][CH:28]=[CH:27][C:22]=2[C:23]([OH:25])=[O:24])=[CH:34][CH:35]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 68869865HCID 68869865, compound

Product 1

HCID 10411648HCID 10411648, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Methyl 2-[(3-{2-[4-(benzyloxy)phenoxy]ethyl}phenoxy)methyl]benzoate (20 mg, 0.043 mmol) was dissolved in a mixture of THF/H2O (7/1, 3 ml) and LiOH (4.1 mg, 0.17 mmol) was added. The reaction was performed in a single node microwave oven (7 min, 150° C.). The mixture was acidified (HCl, 1 ml, 1M) and the water phase washed with two portions of EtOAc (3×5 ml). After removing the solvent by evaporation the crude was purified by preparative HPLC (started with 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). Removing the solvent by evaporation gave 19 mg of 2-[(3-{2-[4-(benzyloxy)phenoxy]ethyl}phenoxy)methyl]benzoic acid (yield 98%).

Workup

  1. additionwas added
  2. customThe reaction was performed in a single node microwave oven
  3. custom(7 min, 150° C.)
  4. washthe water phase washed with two portions of EtOAc (3×5 ml)
  5. customAfter removing the solvent
  6. customby evaporation the crude
  7. customwas 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. additionThe product containing fractions
  12. customthe acetonitrile was removed by evaporation
  13. additionEtOAc (10 ml) was added
  14. washthe organic phase was washed with two portions of brine
  15. dry with materialdried (MgSO4)
  16. customRemoving the solvent
  17. customby evaporation

Sources & evidence

ORD record
ord-0200382911044de19df0c9706b11b84b
Source dataset
uspto-grants-2009_04
Patent number
US07521461B2

Reaction notes

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