Ammonium Chloride → 1-Boc-4-Methylenepiperidine

HRID 1517373Notes

Reaction equation

HRID 1517373 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

Methyltriphenylphosphonium bromide (53.82 g, 150 mmol) was suspended in diethyl ether (300 ml) in a thoroughly heated apparatus flooded with an inert gas and the suspension was 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 the mixture was then warmed to room temperature and stirred for 15 h. The reaction mixture was cooled, ammonium chloride solution (300 ml, 10%) was added, and after separation of the phases the aqueous phase was extracted with ether (3×200 ml) and the combined organic phases were dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) with ether/hexane (1:1). Yield: 18.57 g (93%)

Workup

  1. additionwas slowly added dropwise
  2. temperaturethe mixture was then warmed to room temperature
  3. stirringstirred for 15 h
  4. temperatureThe reaction mixture was cooled
  5. customafter separation of the phases the aqueous phase
  6. extractionwas extracted with ether (3×200 ml)
  7. dry with materialthe combined organic phases were dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (silica gel) with ether/hexane (1:1)

Sources & evidence

ORD record
ord-5de1927ded8c457894c5df0bd15a761b
Source dataset
uspto-grants-2012_07
Patent number
US08232288B2

Reaction notes

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