Triethylamine → 1-[2-(1-Ethylcyclohexyl)ethyl]-4-(5-methylpyridin-2-yl)aminopiperidine

HRID 1820316Notes

Reaction equation

HRID 1820316 reaction equation
C(N(CC)CC)C.Br.Br.[CH3:10][C:11]1[CH:12]=[CH:13][C:14]([NH:17][CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)=[N:15][CH:16]=1.[CH2:24]([C:26]1([CH2:32][CH:33]=O)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[CH3:25].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl-].[NH4+].[OH-].[Na+]>ClCCCl.C(Cl)(Cl)Cl>[CH2:24]([C:26]1([CH2:32][CH2:33][N:21]2[CH2:22][CH2:23][CH:18]([NH:17][C:14]3[CH:13]=[CH:12][C:11]([CH3:10])=[CH:16][N:15]=3)[CH2:19][CH2:20]2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[CH3:25]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 5049666Sodium triacetoxyborohydrideHCID 231098994-(5-Methylpyridin-2-yl)aminopiperidine dihydrobromideHCID 45091813(1-Ethylcyclohexyl)acetaldehyde

Product 1

HCID 231099031-[2-(1-Ethylcyclohexyl)ethyl]-4-(5-methylpyridin-2-yl)aminopiperidineYield 92%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6212ChloroformSolvent2×

Procedure

After adding triethylamine (1.30 mL, 9.06 mmol) to a solution of 4-(5-methylpyridin-2-yl)aminopiperidine dihydrobromide (1.60 g, 4.53 mmol) in 1,2-dichloroethane (7 mL) and stirring the mixture for 30 minutes, a solution of (1-ethylcyclohexyl)acetaldehyde (1.54 g, 4.53 mmol) in 1,2-dichloroethane (8 mL) was added and the mixture was stirred for 15 minutes. Sodium triacetoxyborohydride (0.96 g, 4.53 mmol) was then added while cooling on ice, and after stirring the mixture for 5 minutes, it was further stirred at room temperature for 1 hour. A 25% aqueous ammonium chloride solution, chloroform and 3N aqueous sodium hydroxide were added to the reaction mixture, extraction was performed with chloroform, and the organic layer was washed with saturated aqueous sodium chloride. The organic layer was then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (100 g Merck Art. 9385, chloroform:methanol=95:5) to obtain the title compound as a brown oil (1.37 g, 4.16 mmol) (2 steps, 92% yield).

Workup

  1. stirringthe mixture was stirred for 15 minutes
  2. temperaturewhile cooling on ice
  3. stirringafter stirring the mixture for 5 minutes
  4. stirringit was further stirred at room temperature for 1 hour
  5. washthe organic layer was washed with saturated aqueous sodium chloride
  6. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (100 g Merck Art. 9385, chloroform:methanol=95:5)

Sources & evidence

ORD record
ord-a8ba65e4d2c74bf5a522e095533b5e40
Source dataset
uspto-grants-2009_10
Patent number
US07601843B2

Reaction notes

Loading…