tert-Butyl 4-oxopiperidine-1-carboxylate → 1-Boc-4-Methylenepiperidine

HRID 331123Notes

Reaction equation

HRID 331123 reaction equation
[Li][CH2:2][CH2:3][CH2:4][CH3:5].[C:6]([N:13]1CCC(=O)[CH2:15][CH2:14]1)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[C:9]([O:8][C:6]([N:13]1[CH2:14][CH2:15][C:4](=[CH2:5])[CH2:3][CH2:2]1)=[O:7])([CH3:12])([CH3:11])[CH3:10]

Participants

5

Reactant 2

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 27568081-Boc-4-MethylenepiperidineYield 91%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled suspension of methyl triphenyl phosphonium bromide (47.0 g, 132 mmol) in THF (330 mL) was added n-BuLi (85.0 mL, 136 mmol). 1-Boc-4-piperidone (25.0 g, 125 mmol) was added via cannula as a solution in THF. The resulting mixture was kept at 0° C. and allowed to warm to r.t. over 2 h. The reaction mixture was cooled to 0° C. and quenched with saturated NH4Cl. The resulting precipitate was filtered off and the layers were separated. The remaining aqueous layer was extracted with Et2O and the combined organic layers were dried (MgSO4) and concentrated. The crude residue was purified (FCC) to give 4-methylene-piperidine-1-carboxylic acid tert-butyl ester (22 g, 91%)

Workup

  1. customwas kept at 0° C.
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customquenched with saturated NH4Cl
  4. filtrationThe resulting precipitate was filtered off
  5. customthe layers were separated
  6. extractionThe remaining aqueous layer was extracted with Et2O
  7. dry with materialthe combined organic layers were dried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude residue was purified (FCC)

Sources & evidence

ORD record
ord-d61ea7a09f12471b8c8b59bc85842e25
Source dataset
uspto-grants-2014_11
Patent number
US08877769B2

Reaction notes

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