Ammonium Chloride → 1-Boc-4-Methylenepiperidine

HRID 453899Notes

Reaction equation

HRID 453899 reaction equation
[CH3:1]C([O-])(C)C.[K+].[C:7]([N:14]1[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]1)([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[Cl-].[NH4+]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)C>[CH2:1]=[C:17]1[CH2:18][CH2:19][N:14]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:15][CH2:16]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 27568081-Boc-4-Methylenepiperidine

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

In a heated apparatus flushed with protecting gas, methyltriphenylphosphonium bromide (53.82 g, 150 mmol) was suspended in diethyl ether (300 ml) and cooled to 0° C. Potassium tert-butylate (15.78 g, 140 mmol) was added in portions, and the suspension was stirred for 30 min. Boc-4-piperidone (20 g, 100 mmol), dissolved in diethyl ether (200 ml), was slowly added dropwise, and then the mixture was heated to room temperature and stirred for 15 h. The reaction mixture was cooled, and ammonium chloride solution (300 ml, 10%) was added. After phase separation, the aqueous phase was extracted with ether (3×200 ml), and the combined organic phases were dried (MgSO4) and concentrated under vacuum. The crude product was purified by column chromatography (silica gel) with ether/hexane (1:1). Yield: 18.57 g (93%)

Workup

  1. customIn a heated apparatus flushed
  2. additionwas slowly added dropwise
  3. temperaturethe mixture was heated to room temperature
  4. stirringstirred for 15 h
  5. temperatureThe reaction mixture was cooled
  6. customAfter phase separation
  7. extractionthe aqueous phase was extracted with ether (3×200 ml)
  8. dry with materialthe combined organic phases were dried (MgSO4)
  9. concentrationconcentrated under vacuum
  10. customThe crude product was purified by column chromatography (silica gel) with ether/hexane (1:1)

Sources & evidence

ORD record
ord-9a9e632e824c4e9993f811332aef2d67
Source dataset
uspto-grants-2013_07
Patent number
US08492559B2

Reaction notes

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