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

HRID 2065464Notes

Reaction equation

HRID 2065464 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-2a2993ec58964d6b85f7f70072e87556
Source dataset
uspto-grants-2012_10
Patent number
US08288417B2

Reaction notes

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