Hydrogen Bromide → 1-(4-Bromophenyl)piperidine-4-carboxylic acid

HRID 57588Notes

Reaction equation

HRID 57588 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]([O:16]CC)=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.N([O-])=O.[Na+].[BrH:23]>O>[Br:23][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 260Hydrogen Bromide2×HCID 27641811-(4-Amino-phenyl)-piperidine-4-carboxylic acid ethyl esterHCID 23668193Sodium Nitrite

Product 1

HCID 710936711-(4-Bromophenyl)piperidine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of ethyl 1-(4-aminophenyl)piperidine-4-carboxylate (2.48 g, 10 mmol) in 40 mL of HBr 40%, a solution of NaNO2 (0.69 g, 10 mmol) in 7 mL of water was slowly added at 0° C. The mixture was stirred for 15 minutes and added to a solution of CuBr (0.79 g, 5.5 mmol) in 30 mL of HBr 40%. The resulting mixture was stirred and refluxed for 2 hours. The suspension thus obtained was partitioned between 2N NaOH and ethyl acetate. The organic layer was washed with aqueous NaCl, dried over Na2SO4 and concentrated to afford crude title compound 1.56 g. MS (m/z): 286 (M+2)+

Workup

  1. stirringThe resulting mixture was stirred
  2. temperaturerefluxed for 2 hours
  3. customThe suspension thus obtained
  4. customwas partitioned between 2N NaOH and ethyl acetate
  5. washThe organic layer was washed with aqueous NaCl
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4e1a6d19d4d548d58e0c0bc87587d7a4
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Reaction notes

Loading…