Lithium Hydroxide → 4-(2-Methylpiperidin-1-yl)-3-nitrobenzoic acid

HRID 336229Notes

Reaction equation

HRID 336229 reaction equation
F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[CH3:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][NH:18]1.[OH-].[Li+]>CN(C=O)C.O.C1COCC1>[CH3:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][N:18]1[C:2]1[CH:12]=[CH:11][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14]

Participants

7

Reactant 3

HCID 3939Lithium HydroxideHCID 79742-MethylpiperidineHCID 21277355Ethyl 4-fluoro-3-nitrobenzoate

Product 1

HCID 431767024-(2-Methylpiperidin-1-yl)-3-nitrobenzoic acidYield 94.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Chontech 01072; 1.00 g; 4.69 mmol; 1 eq.) and 2-methylpiperidine (Aldrich M7, 280-3; 1.396 g; 14.07 mmol; 3 eq.) in DMF (4 mL) was stirred at 50° C. for 3 hours. The reaction was then allowed to return to room temperature and diluted with water. Extraction with ethyl acetate, drying over sodium sulfate and concentration in vacuo gave a yellow oil. The oil was taken up in THF (10 mL) and lithium hydroxide (561.73 mg; 23.46 mmol; 5 eq.) was added followed by water (10 mL). The reaction mixture was stirred at room temperature for 16 hours. After evaporation of the THF, the solution was diluted with water and washed with Et2O. The aqueous layer was acidified to pH 5 with AcOH, extracted with Et2O, dried over magnesium sulfate and concentrated in vacuo to afford the title compound (1.17 g, 94%) as a yellow solid.

Workup

  1. customto return to room temperature
  2. extractionExtraction with ethyl acetate
  3. dry with materialdrying over sodium sulfate and concentration in vacuo
  4. customgave a yellow oil
  5. stirringThe reaction mixture was stirred at room temperature for 16 hours
  6. customAfter evaporation of the THF
  7. additionthe solution was diluted with water
  8. washwashed with Et2O
  9. extractionextracted with Et2O
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2d71ca7533954cb4bb90959f32e4b25b
Source dataset
uspto-grants-2014_11
Patent number
US08889668B2

Reaction notes

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