Malononitrile → Tert-butyl 3-{2-amino-6-[2-(benzyloxy)phenyl]-3-cyano-4-pyridinyl}-1-piperidinecarboxylate

HRID 1767339Notes

Reaction equation

HRID 1767339 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15](=O)[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:18]([CH:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1)=O.[C:33](#[N:37])[CH2:34][C:35]#[N:36].C([O-])(=O)C.[NH4+:42]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[NH2:36][C:35]1[C:34]([C:33]#[N:37])=[C:18]([CH:20]2[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]2)[CH:16]=[C:15]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[N:42]=1

Participants

7

Reactant 4

HCID 8010MalononitrileHCID 517165Ammonium AcetateHCID 5205131-[2-(Benzyloxy)phenyl]ethan-1-one2×HCID 99644481-Boc-piperidine-3-carboxaldehyde2×

Product 1

HCID 22258881Tert-butyl 3-{2-amino-6-[2-(benzyloxy)phenyl]-3-cyano-4-pyridinyl}-1-piperidinecarboxylateYield 27%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2′-benzyloxyacetophenone (starting compound 1A) (10.00 g, 44.19 mmol), tert-butyl 3-formyl-1-piperidine carboxylate (starting compound 2B) (10.37 g, 44.61 mmol), malononitrile (3.21 g, 48.61 mmol), and ammonium acetate (17.03 g, 220.97 mmol) in toluene (50 mL) was stirred at 150° C. for 2 hrs. After cooled to room temperature, the reaction mixture was diluted with ethyl acetate. The organic phase was washed with water and saturated brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=2/1). The purified compound (yellow oil) was recrystallized from ethanol to give tert-butyl 3-{2-amino-6-[2-(benzyloxy)phenyl]-3-cyano-4-pyridinyl}-1-piperidinecarboxylate as a white solid. (5.83 g, yield; 27%).

Workup

  1. temperatureAfter cooled to room temperature
  2. washThe organic phase was washed with water and saturated brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (hexane/ethyl acetate=2/1)
  7. customThe purified compound (yellow oil) was recrystallized from ethanol

Sources & evidence

ORD record
ord-9efa4856ef8b400fa00d9266c369b736
Source dataset
uspto-grants-2007_06
Patent number
US07232909B2

Reaction notes

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