Potassium Carbonate → HCID 10783583, compound

HRID 552146Notes

Reaction equation

HRID 552146 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[CH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]([F:25])([F:24])[F:23].C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C1COCC1.[Pd].O.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]([F:25])([F:24])[F:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 67957Benzene, 1-iodo-2-(trifluoromethyl)-HCID 27568081-Boc-4-Methylenepiperidine

Product 1

HCID 10783583HCID 10783583, compoundYield 70%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a degassed sample of 4-methylenepiperidine-1-carboxylic acid tert-butyl ester (0.527 g, 2.67 mmol) was added 9-borabicyclic[3,3,1]nonane (5.6 mL of a 0.5 M solution in THF, 2.8 mmol). The resulting solution was refluxed for 1 hour. After cooling to ambient temperature, the solution was added to a mixture of 1-iodo-2-trifluoromethylbenzene (0.707 mg, 2.600 mmol), Pd-catalyst (3 mol %), DMF (25 mL), water (1 mL), and K2CO3 (0.6 g). The resulting mixture was heated at 60° C. for 3 hours. The mixture was cooled to ambient temperature and then poured into water. The pH of the solution was adjusted to 11 with 10% NaOH solution and the mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine and dried over Na2SO4, filtered, and evaporated to give a crude oil, which was further purified by column chromatography to afford 4-(2-trifluoromethylbenzyl)piperidine-1-carboxylic acid tert-butyl ester as a waxy solid (0.638 g) in 70% yield.

Workup

  1. temperatureThe resulting solution was refluxed for 1 hour
  2. temperatureThe resulting mixture was heated at 60° C. for 3 hours
  3. temperatureThe mixture was cooled to ambient temperature
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give a crude oil, which
  10. customwas further purified by column chromatography

Sources & evidence

ORD record
ord-1ae7f979ae77447baefcdae050bc5e5a
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Reaction notes

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