Sodium hydride → 4-Cyano-3-(3-morpholinopropoxy)aniline

HRID 393654Notes

Reaction equation

HRID 393654 reaction equation
[H-].[Na+].[OH:3][CH2:4][CH2:5][CH2:6][N:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.Cl[C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][C:20]=1[C:21]#[N:22])[NH2:17]>CN1C(=O)CCC1>[C:21]([C:20]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][C:14]=1[O:3][CH2:4][CH2:5][CH2:6][N:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1)#[N:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 887284-Amino-2-chlorobenzonitrileHCID 1995763-Morpholino-1-propanol

Product 1

HCID 2328004-Cyano-3-(3-morpholinopropoxy)anilineYield 26%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
145 °C

Procedure

Sodium hydride (2.0 g of an 85% dispersion in mineral oil, 60 mmol) was added to 4-(3-hydroxypropyl)morpholine (4.8 g, 30 mmol), (Tet. Lett. 1994, 35, 1715), in NMP (50 ml) and the mixture was stirred for 15 minutes. 3-Chloro-4-cyanoaniline (4.8 g, 30 mmol) was added and the mixture was heated at 145° C. for 6 hours. The mixture was allowed to cool and was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and then brine and dried (MgSO4). The solvent was removed by evaporation and the residue was purified by column chromatography eluting with ethyl acetate and then methylene chloride/methanol (9/1) to give 4-cyano-3-(3-morpholinopropoxy)aniline (2.0 g, 26%) as a yellow gum.

Workup

  1. temperatureto cool
  2. customwas partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialbrine and dried (MgSO4)
  6. customThe solvent was removed by evaporation
  7. customthe residue was purified by column chromatography
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-2e4886f4ee0e4197b28e11cf290a84e0
Source dataset
uspto-grants-2004_10
Patent number
US06809097B1

Reaction notes

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