Bromobenzene → (S)-1-Phenylpiperidine-3-carboxylic acid

HRID 656336Notes

Reaction equation

HRID 656336 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([C:15]([OH:17])=[O:16])[CH2:10]1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.O1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:2]1([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([C:15]([OH:17])=[O:16])[CH2:10]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 7961BromobenzeneHCID 312751,4-DioxaneHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 24820453(3S)-piperidine-3-carboxylic acid hydrochloride

Product 1

HCID 66743624(S)-1-Phenylpiperidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A mixture of bromobenzene (0.82 mL, 0.0078 mol), (3S)-piperidine-3-carboxylic acid hydrochloride (6.5 mmol, 0.0065 mol), sodium tert-butoxide (1.2 g, 0.013 mol), palladium acetate (40 mg, 0.0002 mol) and 2-(di-tert-butylphosphino)biphenyl (60 mg, 0.0002 mol) was degassed under vacuum and charged with nitrogen. To the mixture was added 1,4-dioxane (20 mL, 0.2 mol) and the resulting mixture was refluxed overnight. After cooling the reaction mixture to ambient temperature, the mixture was filtered and the filtrate was adjusted with TFA to pH=3.0 and extracted with EtOAc. The crude product was used in the following step without further purification.

Workup

  1. customwas degassed under vacuum
  2. additioncharged with nitrogen
  3. temperaturethe resulting mixture was refluxed overnight
  4. filtrationthe mixture was filtered
  5. extractionextracted with EtOAc
  6. customThe crude product was used in the following step without further purification

Sources & evidence

ORD record
ord-41c51cd26d274050941f5faa7bdd9985
Source dataset
uspto-grants-2011_12
Patent number
US08071624B2

Reaction notes

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