Acetic Acid → 4-((Morpholin-4-yl)methyl)benzonitrile

HRID 1190999Notes

Reaction equation

HRID 1190999 reaction equation
[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1)#[N:2].[NH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCCl>[N:11]1([CH2:7][C:6]2[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 2168644-((Morpholin-4-yl)methyl)benzonitrileYield 79.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Dissolve 4-cyanobenzaldehyde (5 g, 38.1 mmol), morpholine (4.15 g, 47.7 mmol) and acetic acid (2.2 mL, 38.1 mmol) in DCE (100 mL). Add sodium cyanoborohydride (3.59 g, 57.2 mmol), and stir the mixture overnight. Add water (100 mL), separate the layers and extract the aqueous layer with DCM (3×50 mL). Wash the combined organic extracts with brine, dry over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (80 g, pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 1:2 over 1.25 h, 80 mL/min) to obtain the desired intermediate as a colorless oil (6.1 g, 79%). MS (APCI+) m/z: 203 (M+H)+.

Workup

  1. customAdd water (100 mL), separate the layers
  2. extractionextract the aqueous layer with DCM (3×50 mL)
  3. washWash the combined organic extracts with brine
  4. dry with materialdry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by chromatography on silica gel (80 g, pre-packed cartridge)
  8. washeluting with hexane/EtOAc (1:0 to 1:2 over 1.25 h, 80 mL/min)

Sources & evidence

ORD record
ord-58e7650f2a8a4da5968718530d568faf
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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