Potassium Carbonate → 1-(Tert-butoxycarbonyl)-4-(3,4-dichlorobenzyl)piperidine

HRID 331124Notes

Reaction equation

HRID 331124 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][C:11](=[CH2:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].B1C2CCCC1CCC2.Br[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CN(C=O)C.O.O.C1COCC1>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)[CH2:12][CH2:13]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

9

Reactant 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 290134-Bromo-1,2-dichlorobenzeneHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27568081-Boc-4-Methylenepiperidine

Product 1

HCID 222577171-(Tert-butoxycarbonyl)-4-(3,4-dichlorobenzyl)piperidineYield 69%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Procedure

1-Boc-4-methylene piperidine (1.32 g, 6.70 mmol) was degassed (neat) for 15 minutes, and then treated with a THF solution of 9-BBN (0.5 M in THF, 13.5 mL, 6.75 mmol). The reaction mixture was refluxed for 2 h, then cooled to r.t. The reaction mixture was then added, via cannula, to a preformed solution consisting of 4-bromo-1,2-dichlorobenzene (1.49 mg, 6.64 mmol), Pd(dppf)Cl2 dichloromethane complex (148 mg, 0.181 mmol), and potassium carbonate (1.20 g, 8.68 mmol) in DMF/H2O (15 mL/1.5 mL). The resultant mixture was heated at 60° C. for 48 h, cooled to r.t., poured into water, basified to pH 11 with 1N NaOH, and extracted with EtOAc (3×). The organic layers were combined, dried (Na2SO4), and concentrated. The crude residue was purified (FCC) to give 4-(3,4-dichloro-benzyl)-piperidine-1-carboxylic acid tert-butyl ester (1.57 g, 69%).

Workup

  1. temperatureThe reaction mixture was refluxed for 2 h
  2. additionThe reaction mixture was then added, via cannula, to a preformed solution
  3. temperaturecooled to r.t.
  4. extractionextracted with EtOAc (3×)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude residue was purified (FCC)

Sources & evidence

ORD record
ord-903543de63844dcf9ab8f6969ee05a4e
Source dataset
uspto-grants-2014_11
Patent number
US08877769B2

Reaction notes

Loading…