Ammonium Chloride → tert-Butyl 4-(cyanomethylidene)piperidine-1-carboxylate

HRID 1626774Notes

Reaction equation

HRID 1626774 reaction equation
[C:1]([CH2:3]P(=O)(OCC)OCC)#[N:2].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].O=[C:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1.[Cl-].[NH4+]>O1CCCC1>[C:1]([CH:3]=[C:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1)#[N:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 15326949tert-Butyl 4-(cyanomethylidene)piperidine-1-carboxylateYield 108.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Diethyl cyanomethylphosphonate (16 mL, 100 mmol) was dissolved in tetrahydrofuran (360 mL), and a solution of lithium hexamethyldisilazide in tetrahydrofuran (1 M, 100 mL, 100 mmol) and a solution of tert-butyl 4-oxopiperidine-1-carboxylate (18 g, 91 mmol) in tetrahydrofuran (36 mL) were added under a nitrogen atmosphere at −70° C., followed by stirring at the same temperature for 40 minutes. A saturated aqueous ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate, and the extract was washed with a saturated aqueous ammonium chloride solution. After the solvent was distilled off under reduced pressure, the resulting residue was purified by chromatography on a silica gel column (Moritex Corporation, elution solvent: hexane/ethyl acetate), and a fraction corresponding to the Rf value=0.41 (hexane/ethyl acetate=3/1) by thin layer chromatography was concentrated under reduced pressure to afford the title compound (22 g) as a white solid (quantitative yield).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washthe extract was washed with a saturated aqueous ammonium chloride solution
  3. distillationAfter the solvent was distilled off under reduced pressure
  4. customthe resulting residue was purified by chromatography on a silica gel column (Moritex Corporation, elution solvent: hexane/ethyl acetate)
  5. concentrationa fraction corresponding to the Rf value=0.41 (hexane/ethyl acetate=3/1) by thin layer chromatography was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6322356ec8ee42588209803fa3e873ba
Source dataset
uspto-grants-2014_07
Patent number
US08785462B2

Reaction notes

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