Acetic Acid → 4-(piperidin-1-ylmethyl)benzonitrile

HRID 1191003Notes

Reaction equation

HRID 1191003 reaction equation
C([BH3-])#N.[Na+].[C:5]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=1)#[N:6].[NH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.C(O)(=O)C>CO>[N:15]1([CH2:11][C:10]2[CH:13]=[CH:14][C:7]([C:5]#[N:6])=[CH:8][CH:9]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 75376034-(piperidin-1-ylmethyl)benzonitrileYield 54.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Under a nitrogen atmosphere, add sodium cyanoborohydride (5.77 g, 91.6 mmol) to a solution of 4-cyanobenzaldehyde (3 g, 22.9 mmol), piperidine (5.84 g, 68.7 mmol) and acetic acid (2.75 g, 45.8 mmol) in methanol (30 mL) at 0° C. with stirring. Warm the mixture to room temperature and stir overnight. Add water (100 mL), saturated aqueous K2CO3 (50 mL), and extract with DCM. Wash the combined organic extracts with water and brine. Dry the organic phase over Na2SO4, filter, and concentrate in vacuo. Purify by chromatography on silica gel (400 g) eluting with hexane/EtOAc (1:0 to 4:1 gradient) to obtain the desired intermediate as a clear oil (2.48 g, 54%). MS (APCI+) m/z: 201 (M+H)+.

Workup

  1. stirringstir overnight
  2. extractionAdd water (100 mL), saturated aqueous K2CO3 (50 mL), and extract with DCM
  3. washWash the combined organic extracts with water and brine
  4. dry with materialDry the organic phase over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by chromatography on silica gel (400 g)
  8. washeluting with hexane/EtOAc (1:0 to 4:1 gradient)

Sources & evidence

ORD record
ord-67f9a992c6344b3bac0d680cfafb51b6
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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