Ethyl 4-cyclohexyl-4-piperidinecarboxylate → (4-Cyclohexylpiperidin-4-yl)-methanol

HRID 1795163Notes

Reaction equation

HRID 1795163 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C([O:9][C:10]([C:12]1([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)=O)C>O1CCCC1>[CH:18]1([C:12]2([CH2:10][OH:9])[CH2:13][CH2:14][NH:15][CH2:16][CH2:17]2)[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

4

Reactant 2

HCID 18418945Ethyl 4-cyclohexyl-4-piperidinecarboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 22185324(4-Cyclohexylpiperidin-4-yl)-methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (−5° C.) solution of lithium aluminum hydride (900 mL, 0.90 moles, 1.0M solution in THF) is added tetrahydrofuran (2000 mL) and 4-cyclohexyl-piperidine-4-carboxylic acid ethyl ester, 1, (59.5 g, 249 mmol). The resulting solution is stirred at between −5° C. and +3° C. for 1 hour and then allowed to warmed to room temperature and stir an additional sixty-six hours. The reaction is then re-cooled to 0° C. and carefully quenched with saturated ammonium chloride (100 mL). The reaction mixture is stirred for 10 minutes and then 87:10:3 ethyl acetate:methanol:triethylamine (500 mL) is added. The suspension is then stirred at room temperature for 20 minutes and filtered through a pad of Celite. The solids are re-suspended in 1:1 THF:EtOAc (2000 mL), stirred at room temperature for 1 hour and the suspension was again filtered through a pad of Celite. The filtrates are combined and concentrated in vacuo to afford 53.6 g of a mixture of the desired compound and 4-cyclohexyl-piperidine-4-carbaldehyde. The crude mixture is used directly in without further purification.

Workup

  1. stirringstir an additional sixty-six hours
  2. temperatureThe reaction is then re-cooled to 0° C.
  3. customcarefully quenched with saturated ammonium chloride (100 mL)
  4. stirringThe reaction mixture is stirred for 10 minutes
  5. addition87:10:3 ethyl acetate:methanol:triethylamine (500 mL) is added
  6. stirringThe suspension is then stirred at room temperature for 20 minutes
  7. filtrationfiltered through a pad of Celite
  8. stirringEtOAc (2000 mL), stirred at room temperature for 1 hour
  9. filtrationthe suspension was again filtered through a pad of Celite
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fa8101b6d5d842faadcad1bae0fa8c77
Source dataset
uspto-grants-2006_04
Patent number
US07026335B2

Reaction notes

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