Ammonium Chloride → 1-Boc-4-Methylenepiperidine

HRID 1808361Notes

Reaction equation

HRID 1808361 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 thoroughly heated apparatus flooded with protecting gas, methyltriphenyl-phosphonium 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 warmed to room temperature and stirred for 15 h. The reaction mixture was cooled, and ammonium chloride solution (300 ml, 10%) was added thereto; after phase separation, 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 warmed to room temperature
  3. stirringstirred for 15 h
  4. temperatureThe reaction mixture was cooled
  5. customafter phase separation
  6. extractionthe aqueous phase was 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-3cd445caa33c4da8a39d89a82ac4ce5e
Source dataset
uspto-grants-2013_01
Patent number
US08357717B2

Reaction notes

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