Lithium Hydroxide → 4-[(R)-3-(2-methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid

HRID 1617795Notes

Reaction equation

HRID 1617795 reaction equation
C[O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([C@H:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])[CH2:11][C:12]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=2)=[O:13])=[CH:6][CH:5]=1.[OH-].[Li+].[Cl-].[NH4+].C(OCC)(=O)C>O1CCCC1>[CH3:20][C:16]1[CH:15]=[C:14]([C:12](=[O:13])[CH2:11][C@H:10]([C:7]2[CH:6]=[CH:5][C:4]([C:3]([OH:28])=[O:2])=[CH:9][CH:8]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])[CH:19]=[CH:18][N:17]=1

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 666668344-[(R)-3-(2-Methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid methyl ester

Product 1

HCID 666665574-[(R)-3-(2-methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-[(R)-3-(2-methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid methyl ester (98 mg) in tetrahydrofuran (3 mL) was added 1 M aq. lithium hydroxide solution (2.62 mL). The reaction mixture was stirred at room temperature for 4 h. A saturated aq. solution of ammonium chloride and ethyl acetate were added, the phases were separated and the inorganic one was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to yield 4-[(R)-3-(2-methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzoic acid as a white solid. This was reacted in analogy to example 132, step 6 with hydroxylamine hydrochloride in the presence of sodium hydrogencarbonate to afford the title compound as a white solid (98 mg, 60%), MS (ESI−): m/z=372.9 ([M−H]−).

Workup

  1. customthe phases were separated
  2. extractionthe inorganic one was extracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b2976388a81a4b0a8289b002ab4aa2b5
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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