Triethylamine → 1-(3-Tert-butyldimethylsiloxy-3-cyclohexylpropyl)-4-(5-methylpyridin-2-yl)aminopiperidine

HRID 1820302Notes

Reaction equation

HRID 1820302 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH:9]1([CH:15]([OH:32])[CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][CH:21]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][N:26]=3)[CH2:20][CH2:19]2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[O:32]([CH:15]([CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][CH:21]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][N:26]=2)[CH2:22][CH2:23]1)[Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 231099131-(3-Cyclohexyl-3-hydroxypropyl)-4-(5-methylpyridin-2-yl)aminopiperidine

Product 1

HCID 231099081-(3-Tert-butyldimethylsiloxy-3-cyclohexylpropyl)-4-(5-methylpyridin-2-yl)aminopiperidineYield 77.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

After adding tert-butyldimethylsilyl chloride (203 mg, 1.5 mmol) to a solution of 1-(3-cyclohexyl-3-hydroxypropyl)-4-(5-methylpyridin-2-yl)aminopiperidine (405 mg, 1.22 mmol), triethylamine (0.20 mL) and 4-dimethylaminopyridine (30 mg, 0.24 mmol) in methylene chloride (5 mL) while cooling on ice, the mixture was stirred at room temperature for 18 hours. Triethylamine (0.20 mL), 4-dimethylaminopyridine (30 mg, 1.5 mmol) and tert-butyldimethylsilyl chloride (203 mg, 1.5 mmol) were further added to the reaction mixture and stirring was continued at room temperature for 70 hours. NH silica Chromatorex DM1020 was added to the reaction mixture, which was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (60 g NH silica Chromatorex DM2035, hexane:ethyl acetate=4:1) to obtain the title compound as a colorless oil (423 mg) (77.7% yield).

Workup

  1. temperaturewhile cooling on ice
  2. stirringstirring
  3. waitwas continued at room temperature for 70 hours
  4. additionNH silica Chromatorex DM1020 was added to the reaction mixture, which
  5. concentrationwas then concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (60 g NH silica Chromatorex DM2035, hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-d7d77854b8c8499a91141883bbe65d6f
Source dataset
uspto-grants-2009_10
Patent number
US07601843B2

Reaction notes

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