Methanol → 8-Benzyl-6-hydroxy-2,8-diazaspiro[4.5]decan-1-one

HRID 1501794Notes

Reaction equation

HRID 1501794 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([CH2:19][C:20]#[N:21])([C:14](OCC)=[O:15])[C:10](=[O:22])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO>[Pt]=O.C(O)(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([C:14](=[O:15])[NH:21][CH2:20][CH2:19]2)[CH:10]([OH:22])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 86709485Ethyl 1-benzyl-4-(cyanomethyl)-3-oxopiperidine-4-carboxylate

Product 1

HCID 867094868-Benzyl-6-hydroxy-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 2

HCID 82844Platinum oxide (PtO)CatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

To a flask charged with ethyl 1-benzyl-4-(cyanomethyl)-3-oxopiperidine-4-carboxylate (900 mg, 3.0 mmol) and a stir bar was added platinum oxide (100 mg, 0.44 mmol), MeOH (20 mL) and acetic acid (20 mL). The mixture was allowed to stir vigorously under an atmosphere of hydrogen for 24 hours. LC indicated complete reaction at that point. The catalyst was removed by filtration through a pad of CELITE®, and the filtrate was concentrated under reduced pressure. The residue was dissolved in EtOH (100 mL), and K2CO3 was added (2.1 g, 15 mmol). The mixture was heated to 90° C. for 4 hours. The reaction was cooled, and DCM was added (200 mL) to precipitate the solids. The solids were then removed by filtration, and the crude reaction was adsorbed onto silica gel, and flushed out with DCM and 10% MeOH (mixed with 10% NH4OH) to give the title compound. LCMS: m/z 261 (M+H)+.

Workup

  1. customreaction at that point
  2. customThe catalyst was removed by filtration through a pad of CELITE®
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in EtOH (100 mL)
  5. additionK2CO3 was added (2.1 g, 15 mmol)
  6. temperatureThe reaction was cooled
  7. additionDCM was added (200 mL)
  8. customto precipitate the solids
  9. customThe solids were then removed by filtration
  10. customthe crude reaction
  11. customflushed out with DCM and 10% MeOH (mixed with 10% NH4OH)

Sources & evidence

ORD record
ord-f2683040793e4bc98b58b50eace39826
Source dataset
uspto-grants-2015_12
Patent number
US09206198B2

Reaction notes

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