Acetic Acid → 4-(IsopropylaMino-Methyl)-benzonitrile

HRID 1191014Notes

Reaction equation

HRID 1191014 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].[CH:15]([NH2:18])([CH3:17])[CH3:16].C(O)(=O)C>CO>[CH:15]([NH:18][CH2:11][C:10]1[CH:13]=[CH:14][C:7]([C:5]#[N:6])=[CH:8][CH:9]=1)([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6363IsopropylamineHCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 201186114-(IsopropylaMino-Methyl)-benzonitrileYield 38.3%

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), iso-propylamine (2.03 g, 34.4 mmol) and acetic acid (1.37 g, 22.9 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 (300 g) eluting with 9:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) to obtain the desired intermediate (1.53 g, 38%). MS (APCI+) m/z: 175 (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 (300 g)
  8. washeluting with 9:1 DCM/(chloroform:methanol:concentrated NH4OH 80:18:2)

Sources & evidence

ORD record
ord-fff4047f79da4485850c7c3cbc795de9
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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