Potassium Carbonate → 3-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1909080Notes

Reaction equation

HRID 1909080 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10](=[CH2:14])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].B1C2CCCC1CCC2.Br[C:25]1[CH:35]=[CH:34][C:28]2[O:29][C:30]([F:33])([F:32])[O:31][C:27]=2[CH:26]=1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O.C1COCC1>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][C:35]2[CH:25]=[CH:26][C:27]3[O:31][C:30]([F:32])([F:33])[O:29][C:28]=3[CH:34]=2)[CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27362715-Bromo-2,2-difluoro-1,3-benzodioxoleHCID 112525943-Methylene-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673899963-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperidine-1-carboxylic acid tert-butyl esterYield 67%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Procedure

1-Boc-3-methylene piperidine (842 mg, 4.27 mmol) was degassed (neat) for 15 minutes and then treated with a THF solution of 9-BBN (0.5 M in THF, 8.6 mL, 4.3 mmol). The reaction mixture was refluxed for 2 h, then cooled to rt. The reaction mixture was then added, via cannula, to a preformed solution of 5-bromo-2,2-difluoro-1,3-benzodioxole (1.00 g, 4.22 mmol), Pd(dppf)Cl2—CH2Cl2 (94 mg, 0.128 mmol), and potassium carbonate (746 mg, 5.40 mmol) in DMF/H2O (10 mL/1 mL). The resultant mixture was heated at 60° C. for 18 h, cooled to rt, poured into water, basified to pH 11 with 1 N NaOH, and extracted with EtOAc (3×). The organic layers were combined, dried (Na2SO4), and concentrated. The crude residue was purified (FCC) to give 3-(2,2-difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperidine-1-carboxylic acid tert-butyl ester (1.00 g, 67%).

Workup

  1. temperatureThe reaction mixture was refluxed for 2 h
  2. temperaturecooled to rt
  3. extractionextracted with EtOAc (3×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude residue was purified (FCC)

Sources & evidence

ORD record
ord-47519a3e6fbf452ebb6137fe47a30e0f
Source dataset
uspto-grants-2013_12
Patent number
US08598356B2

Reaction notes

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