4-Amino-1-methylpiperidine → HCID 67049882, compound

HRID 885829Notes

Reaction equation

HRID 885829 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:26])/[CH:9]=[CH:10]/[C:11]2[CH:16]=[CH:15][C:14](/[CH:17]=[CH:18]/[C:19]([O:21]C(C)(C)C)=[O:20])=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.[CH3:27][N:28]1[CH2:33][CH2:32][CH:31]([NH2:34])[CH2:30][CH2:29]1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:27][N:28]1[CH2:33][CH2:32][CH:31]([NH:34][C:2]2[CH:3]=[CH:4][C:5]([C:8](=[O:26])/[CH:9]=[CH:10]/[C:11]3[CH:12]=[CH:13][C:14](/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20])=[CH:15][CH:16]=3)=[CH:6][CH:7]=2)[CH2:30][CH2:29]1

Participants

6

Reactant 3

HCID 27375314-Amino-1-methylpiperidineHCID 23676156Sodium t-butoxideHCID 49818132HCID 49818132, compound

Product 1

HCID 67049882HCID 67049882, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (±)BINAP (435 mg, 0.7 mmol) and Pd2(dba)3 (320 mg, 0.35 mmol) in toluene (10 ml) was heated to 80° C. for 1 h under N2. Then the mixture was cooled down to room temperature and tert-butyl (E)-3-{4-[(E)-3-(4-bromo-phenyl)-3-oxo-propenyl]-phenyl}-acrylate (726 mg, 1.75 mmol), 1-methyl-piperidin-4-ylamine (0.200, 1.75 mmol) and NaOtBu (252 mg, 2.6 mmol) were added. The reaction was refluxed overnight under N2, then the slurry was filtrated (Celite) and the organic filtrate was evaporated in vacuo. The crude reaction mixture was purified by column chromatography (eluent: petroleum ether/AcOEt 1:1). The resulting product was dissolved in DCM (1 ml) and TFA (1 ml) and the solution was stirred at room temperature for 4 h. The solvent was removed in vacuo to give 280 mg of (E)-3-(4-{(E)-3-[4-(1-methyl-piperidin-4-ylamino)-phenyl]-3-oxo-propenyl}-phenyl)-acrylic acid as its trifluoroacetate salt.

Workup

  1. temperatureThen the mixture was cooled down to room temperature
  2. temperatureThe reaction was refluxed overnight under N2
  3. filtrationthe slurry was filtrated (Celite)
  4. customthe organic filtrate was evaporated in vacuo
  5. customThe crude reaction mixture
  6. customwas purified by column chromatography (eluent: petroleum ether/AcOEt 1:1)
  7. dissolutionThe resulting product was dissolved in DCM (1 ml)
  8. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-4c211f56da8a4b89af448d2f77b13047
Source dataset
uspto-grants-2012_08
Patent number
US08242175B2

Reaction notes

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