Hydrochloric Acid → (R)-4-(2-methylphenyl)-4-(2-nitro-5-(3-pyridylmethoxy)phenoxy)butanoic acid

HRID 322902Notes

Reaction equation

HRID 322902 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]([O:18][C:19]1[CH:24]=[C:23]([O:25][CH2:26][C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)[CH:22]=[CH:21][C:20]=1[N+:33]([O-:35])=[O:34])[CH2:9][CH2:10][C:11]([O:13]C(C)(C)C)=[O:12].[OH-].[Na+].O.Cl>CO.CCCCC>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]([O:18][C:19]1[CH:24]=[C:23]([O:25][CH2:26][C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)[CH:22]=[CH:21][C:20]=1[N+:33]([O-:35])=[O:34])[CH2:9][CH2:10][C:11]([OH:13])=[O:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 53646282tert-butyl (R)-4-(2-methylphenyl)-4-(2-nitro-5-(3-pyridylmethoxy)phenoxy)butanoate

Product 1

HCID 54169755(R)-4-(2-methylphenyl)-4-(2-nitro-5-(3-pyridylmethoxy)phenoxy)butanoic acidYield 21.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8003PentaneSolvent

Procedure

A solution of tert-butyl (R)-4-(2-methylphenyl)-4-(2-nitro-5-(3-pyridylmethoxy)phenoxy)butanoate (800 mg) in methanol (20 mL) containing 5 N sodium hydroxide (10 mL) is stirred at ambient temperature for 48 hours. The reaction mixture is poured into water (50 mL), acidified to pH 5 with 1 N HCl and extracted three times with ethyl acetate (50 mL). The combined organic phases are washed with brine (50 mL), dried over magnesium sulphate, filtered and concentrated under reduced pressure The residual brown gum is purified by flash chromatography on silica eluting with ethyl acetate. Fractions homogeneous in the required product are combined and evaporated to give a yellow oil. Trituration with pentane afforded (R)-4-(2-methylphenyl)-4-(2-nitro-5-(3-pyridylmethoxy)phenoxy)butanoic acid as a white solid (150 mg), m.p. 117-119° C. [Elemental analysis:- C,65.4, H, 5.21, N, 6.64%. Calculated:- C,65.3, H, 5.17, N, 6.59%]

Workup

  1. extractionextracted three times with ethyl acetate (50 mL)
  2. washThe combined organic phases are washed with brine (50 mL)
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure The residual brown gum
  6. customis purified by flash chromatography on silica eluting with ethyl acetate
  7. customevaporated
  8. customto give a yellow oil

Sources & evidence

ORD record
ord-228863ac08974c198ad0a97e112ba72b
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Reaction notes

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