Acetic Acid → 4-(Benzylamino)cyclohexan-1-one

HRID 518637Notes

Reaction equation

HRID 518637 reaction equation
O1[C:5]2([CH2:10][CH2:9][C:8](=[O:11])[CH2:7][CH2:6]2)OCC1.[C:12]1([CH2:18][NH2:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCCl.[OH-].[Na+].C(Cl)Cl>[CH2:18]([NH:19][CH:5]1[CH2:6][CH2:7][C:8](=[O:11])[CH2:9][CH2:10]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 7504BenzylamineHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 159326254-(Benzylamino)cyclohexan-1-oneYield 69.9%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a suspension of 1,4-dioxaspiro[4.5]decan-8-one (10 g, 64.0 mmol) in DCE (200 mL) was added phenylmethanamine (7.34 mL, 67.2 mmol), AcOH (3.67 mL, 64.0 mmol) and sodium triacetoxyborohydride (19.00 g, 90 mmol). The reaction was stirred at RT for 16 hours and then the mixture was diluted with 1N NaOH (100 mL) and DCM (250 mL). The organic layer was collected, dried over sodium sulfate and concentrated under reduced pressure. The residue was suspended in acetone (66.7 mL) and treated with HCl (2N aqueous) (64.0 mL, 128 mmol), and the mixture was stirred at RT for 16 hours. The reaction mixture was concentrated to half its volume and diluted with 1 N aqueous NaOH (100 mL) and DCM (300 mL). The layers were separated, and the organic portion was dried over sodium sulfate and concentrated under reduced pressure to afford a white solid. The solid was purified by silica gel chromatography (5-10% MeOH/DCM) to afford 4-(benzylamino)cyclohexanone (9.1 g, 69.9% yield). MS m/z=204.2 [M+H]. Calc'd for C13H17NO: 203.1.

Workup

  1. customThe organic layer was collected
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. stirringthe mixture was stirred at RT for 16 hours
  5. concentrationThe reaction mixture was concentrated to half its volume
  6. additiondiluted with 1 N aqueous NaOH (100 mL) and DCM (300 mL)
  7. customThe layers were separated
  8. dry with materialthe organic portion was dried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customto afford a white solid
  11. customThe solid was purified by silica gel chromatography (5-10% MeOH/DCM)

Sources & evidence

ORD record
ord-887824f48edd4b6d9bbc7f0ef232491a
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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