Dimethylformamide → Piperidine

HRID 1195082Notes

Reaction equation

HRID 1195082 reaction equation
BrBr.[CH3:3][O:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.[CH2:15]([O:22][C:23]1C=CC(O)=CC=1)[C:16]1C=CC=CC=1.COCCCl.C(OC1C=CC(OCCOC)=CC=1)C1C=CC=CC=1.BrC1C=C(OCCOC)C=CC=1O.C(=O)([O-])[O-].[K+].[K+].C(Br)C1C=CC=CC=1.C(OC1C=CC(OCCOC)=CC=1Br)C1C=CC=CC=1.[CH3:101][N:102](C)C=O>C(Cl)(Cl)Cl.[Pd].CO.CC(C)=O>[NH:102]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.[O:4]1[CH2:3][CH:5]1[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:16][CH2:15][O:22][CH3:23])=[CH:10][C:9]=1[C:101]#[N:102]

Participants

16

Reactant 10

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 7638MonobenzoneHCID 11430Potassium CarbonateHCID 123162-Chloroethyl methyl etherHCID 24408BromineHCID 133135614-(2-Methoxyethoxy)phenolHCID 133135622-Bromo-4-(2-methoxyethoxy)phenolHCID 133135631-Benzyloxy-2-bromo-4-(2-methoxyethoxy)benzeneHCID 133135851-Benzyloxy-4-(2-methoxyethoxy)benzene

Product 2

HCID 8082PiperidineHCID 13313566HCID 13313566, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 180AcetoneSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

Bromine dissolved in chloroform is added at 0° to a solution of 4-(2-methoxyethoxy)phenol (M.P. 98°-99°) [prepared by reacting 4-benzyloxyphenol with 2-chloroethyl methyl ether and debenzylating the resultant 1-benzyloxy-4-(2-methoxyethoxy)benzene (M.P. 41°-43°) by hydrogenation with palladium on charcoal] in methanol and the mixture stirred for 2 hours. After chromatography over silicagel, the resultant 2-bromo-4-(2-methoxyethoxy)phenol (oil) is reacted for 60 hours with a mixture of potassium carbonate, acetone and benzyl bromide. After chromatography over silicagel, the resultant 1-benzyloxy-2-bromo-4-(2-methoxyethoxy)benzene (oil) is reacted in dimethylformamide for 5 hours with cuprous cyanide. After purification by partition between aqueous hydrochloric acid solution and ethyl acetate, the resultant 2-benzyloxy-5-(2-methoxyethoxy)benzonitrile (M.P. 50°-51° ) is debenzylated over 10% palladium on charcoal in methanol. The resultant 2-hydroxy-5-(2-methoxyethoxy)benzonitrile (oil) is reacted at 100° with epichlorhydrin and a catalytic amount of piperidine, and 2-(2,3-epoxypropoxy)-5-(2-methoxyethoxy)benzonitrile (oil) is obtained.

Workup

  1. customprepared
  2. customAfter purification
  3. customby partition between aqueous hydrochloric acid solution and ethyl acetate
  4. customThe resultant 2-hydroxy-5-(2-methoxyethoxy)benzonitrile (oil) is reacted at 100° with epichlorhydrin

Sources & evidence

ORD record
ord-87e0db92a2a94adca77edec935fbdd4d
Source dataset
uspto-grants-1989_03
Patent number
US04816604

Reaction notes

Loading…