2-Chloropropane → 1-Benzyl-4-(pyridin-3-YL)piperidin-4-OL

HRID 1643432

Reaction equation

HRID 1643432 reaction equation
[Mg].BrC(Br)C.C(Cl)(C)C.Br[C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1.[CH2:17]([N:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O1CCCC1.C(Cl)(Cl)Cl.O.CO.CCOCC>[CH2:17]([N:24]1[CH2:29][CH2:28][C:27]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)([OH:30])[CH2:26][CH2:25]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

11

Reactant 5

HCID 63612-ChloropropaneHCID 112011,1-DibromoethaneHCID 122863-BromopyridineHCID 192201-Benzyl-4-piperidoneHCID 5462224Magnesium2×

Product 1

HCID 10940791-Benzyl-4-(pyridin-3-YL)piperidin-4-OL

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

(Apparatus: 1 I three-necked flask with nitrogen balloon) Magnesium (5.7 g) was initially introduced into anhydrous ether (125 ml), 1,1-dibromoethane (0.5 g) and isopropyl chloride (17.3 ml) were added dropwise and the mixture was stirred for 15 min to initiate the magnesium. A solution of 3-bromopyridine (25 g) in anhydrous tetrahydrofuran (400 ml) was added dropwise at 40° C. over the course of 20 min and the mixture was then refluxed for 2 h. A solution of 1-benzylpiperidin-4-one (30 g) in anhydrous tetrahydrofuran (100 ml) was finally added dropwise at 40° C. over the course of 20 min and the mixture was stirred at room temperature overnight. Thin layer chromatography control: 10% methanol in chloroform. The reaction mixture was hydrolysed with water (50 ml) at 0° C. and filtered over Celite. Extraction was carried out with methylene chloride (2×100 ml) and the combined organic phases were washed with water (50 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (Alox neutral) with 5% methanol in chloroform. Yield: 8.2 g (19%)

Workup

  1. additionwere added dropwise
  2. temperaturethe mixture was then refluxed for 2 h
  3. stirringthe mixture was stirred at room temperature overnight
  4. filtrationfiltered over Celite
  5. extractionExtraction
  6. washthe combined organic phases were washed with water (50 ml)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (Alox neutral) with 5% methanol in chloroform

Sources & evidence

ORD record
ord-8bda3eca92724b44aa900d46182fdf71
Source dataset
uspto-grants-2012_02
Patent number
US08119805B2

Linked notes

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