Hydrochloric Acid → US9249085, I(ai)

HRID 1771787Notes

Reaction equation

HRID 1771787 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][C:8]([O:10]C(C)C)=[O:9])=[C:4]([CH3:16])[C:3]=1[NH:17][CH2:18][C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)[C:20]=1[F:33].[OH-].[Na+].Cl>C1COCC1.O>[F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][C:8]([OH:10])=[O:9])=[C:4]([CH3:16])[C:3]=1[NH:17][CH2:18][C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)[C:20]=1[F:33]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 89445459Isopropyl 2-[4-fluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]-2-methyl-phenoxy]acetate

Product 1

HCID 89443584US9249085, I(ai)Yield 10%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of isopropyl 2-[4-fluoro-3-[[2-fluoro-3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]-2-methyl-phenoxy]acetate (100 mg, 0.22 mmol, 1.0 eq) in a mixture of THF (10 mL) and H2O (10 mL) was added NaOH (17 mg, 0.44 mmol, 2.0 eq). The reaction was stirred for 2 h then acidified to pH 4 by addition of 1M HCl. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (CH2Cl2:MeOH, 20:1) to give a partially purified material. Further purification by preparative HPLC provided the title compound as yellow solid (9 mg, 10%).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc
  2. washthe combined organic extracts were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue obtained
  7. customwas purified by column chromatography (CH2Cl2:MeOH, 20:1)
  8. customto give a partially purified material
  9. customFurther purification by preparative HPLC

Sources & evidence

ORD record
ord-4c3d77dea12a49b5bfadd33226cda2ab
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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