Lithium Hydroxide → 3-Cyano-4-(2-methylpiperidin-1-yl)benzoic acid

HRID 336256

Reaction equation

HRID 336256 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][NH:3]1.[C:8]([C:10]1[CH:11]=[C:12]([CH:17]=[CH:18][C:19]=1F)[C:13]([O:15]C)=[O:14])#[N:9].[Li+].[OH-]>CN(C=O)C.O>[C:8]([C:10]1[CH:11]=[C:12]([CH:17]=[CH:18][C:19]=1[N:3]1[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]1[CH3:1])[C:13]([OH:15])=[O:14])#[N:9]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 79742-MethylpiperidineHCID 45790123Methyl 3-cyano-4-fluorobenzoate

Product 1

HCID 594957013-Cyano-4-(2-methylpiperidin-1-yl)benzoic acidYield 80.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

2-Methylpiperidine (744 mg; 7.5 mmol; 5 eq.) was added to a solution of methyl 3-cyano-4-fluorobenzoate (269 mg; 1.5 mmol; 1 eq.) in DMF (2 mL) and the resulting mixture was stirred at room temperature for 2 days. The solution was partitioned between ethyl acetate and water and the phases separated. The organic layer was washed with HCl 0.1M then brine, dried over magnesium sulfate and concentrated in vacuo. The residue was taken up in THF (5 mL) and LiOH (126 mg; 3 mmol; 2 eq.) then water (5 mL) were added and the reaction mixture was stirred at room temperature for 5 hours. The resulting solution was diluted with water and washed with Et2O. The aqueous layer was acidified to pH 2 with HCl 0.1M and extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and concentrated in vacuo to afford the title compound (294 mg, 80%) as an off-white solid.

Workup

  1. customThe solution was partitioned between ethyl acetate and water
  2. customthe phases separated
  3. washThe organic layer was washed with HCl 0.1M
  4. dry with materialbrine, dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. stirringthe reaction mixture was stirred at room temperature for 5 hours
  7. washwashed with Et2O
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic phase was dried over magnesium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6bc00f824d174c799cec5f645b14d410
Source dataset
uspto-grants-2014_11
Patent number
US08889668B2

Linked notes

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