4-[Benzyl(methyl)amino]cyclohexan-1-one → 4-(Benzyl(methyl)amino)-1-(2-(dimethylamino)pyridin-4-yl)cyclohexanol

HRID 1193403Notes

Reaction equation

HRID 1193403 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([N:13]([CH3:15])[CH3:14])[CH:8]=1.[CH2:16]([N:23]([CH3:31])[CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(OCC)C>[CH2:16]([N:23]([CH3:31])[CH:24]1[CH2:29][CH2:28][C:27]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([N:13]([CH3:15])[CH3:14])[CH:8]=2)([OH:30])[CH2:26][CH2:25]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 220099204-[Benzyl(methyl)amino]cyclohexan-1-oneHCID 234369354-Bromo-N,N-dimethylpyridin-2-amineHCID 178418339Butyllithium

Product 1

HCID 667992224-(Benzyl(methyl)amino)-1-(2-(dimethylamino)pyridin-4-yl)cyclohexanolYield 71%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

n-BuLi (3 ml, 5.98 mmol, 1.2 eq., 2 M solution in hexane) was added at −78° C. to a solution of 4-bromo-N,N-dimethylpyridin-2-amine (978 mg, 5.23 mmol, 1.05 eq.) in diethyl ether (15 ml) and the mixture was stirred for 45 minutes. A solution of 4-(benzyl(methyl)amino)cyclo-hexanone (stage 3, AMN-50) (1.08 g, 4.9, 8 mmol 1.0 eq.) in diethyl ether (10 ml) was added dropwise thereto at the same temperature. The reaction mixture was stirred for 16 hours at RT and was then hydrolyzed with sat. ammonium chloride solution (30 ml) and extracted with ethyl acetate (3×60 ml). The combined org. phases were washed with sat. NaCl solution (100 ml), dried over sodium sulfate, concentrated and purified by column chromatography (silica gel, 2,5% MeOH in DCM). Yield: 71% (1.20 g, 3.54 mmol)

Workup

  1. stirringThe reaction mixture was stirred for 16 hours at RT
  2. extractionhydrolyzed with sat. ammonium chloride solution (30 ml) and extracted with ethyl acetate (3×60 ml)
  3. washphases were washed with sat. NaCl solution (100 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by column chromatography (silica gel, 2,5% MeOH in DCM)

Sources & evidence

ORD record
ord-cdc17ed0fd8346a1a39954acc13f5bbc
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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