Sodium hydride → HCID 18933638, compound

HRID 1598310Notes

Reaction equation

HRID 1598310 reaction equation
[CH2:1]([N:8]([CH3:12])[CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Cl:15][C:16]1[CH:23]=[CH:22][CH:21]=[C:20](F)[C:17]=1[C:18]#[N:19]>CN(C=O)C.CCOCC>[CH2:1]([N:8]([CH2:9][CH2:10][O:11][C:20]1[CH:21]=[CH:22][CH:23]=[C:16]([Cl:15])[C:17]=1[C:18]#[N:19])[CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 66876N-Benzyl-N-methylethanolamineHCID 695872-Chloro-6-fluorobenzonitrile

Product 1

HCID 18933638HCID 18933638, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent3×

Procedure

A solution of N-benzyl-N-methylethanolamine (145 g) in dry DMF (500 ml) was added dropwise to a stirred suspension of sodium hydride (35.15 g of a 60% dispersion in mineral oil) in dry DMF (1000 ml) over 20 minutes under nitrogen. The mixture was heated on a steam bath for 30 minutes to give a solution. The solution was cooled to ambient temperature and a solution of 2-chloro-6-fluorobenzonitrile (136.7 g) in dry DMF (300 ml) was added over 30 minutes with stirring. The mixture was heated on a steam bath for 3 hours with stirring and distilled at approximately 13 mbar to remove 1 liter of DMF. The residue was cooled to ambient temperature and poured into ice (2 l), basified with 5M sodium hydroxide solution to pH 14 and extracted with dichloromethane to give an oil. This oil was dissolved in ether (2 l) and washed with water (4×200 ml). The ether solution was extracted with 2M hydrochloric acid (500 ml) which gave three layers in the separating funnel. The bottom two layers were run off and the top ether layer was extracted with 2M hydrochloric acid (2×250 ml). The combined acidic layers were basified with concentrated sodium hydroxide solution with cooling and then extracted with dichloromethane to give 2-[2-(N-benzyl-N-methylamino)ethoxy]-6-chlorobenzonitrile as an oil.

Workup

  1. temperatureThe mixture was heated on a steam bath for 30 minutes
  2. customto give a solution
  3. temperatureThe mixture was heated on a steam bath for 3 hours
  4. stirringwith stirring
  5. distillationdistilled at approximately 13 mbar
  6. customto remove 1 liter of DMF
  7. temperatureThe residue was cooled to ambient temperature
  8. additionpoured into ice (2 l)
  9. extractionextracted with dichloromethane
  10. customto give an oil
  11. washwashed with water (4×200 ml)
  12. extractionThe ether solution was extracted with 2M hydrochloric acid (500 ml) which
  13. customgave three layers in the separating funnel
  14. extractionthe top ether layer was extracted with 2M hydrochloric acid (2×250 ml)
  15. temperaturewith cooling
  16. extractionextracted with dichloromethane

Sources & evidence

ORD record
ord-a1988f90ad444313a4a4fa109c3f09df
Source dataset
uspto-grants-1998_04
Patent number
US05736568

Reaction notes

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