Benzyl Bromide → Piperidine

HRID 2226339Notes

Reaction equation

HRID 2226339 reaction equation
C(OC1C=CC(OCCOCC2CC2)=CC=1)C1C=CC=CC=1.[C:23]([C:25]1[CH:48]=[C:47]([O:49][CH2:50][CH2:51][O:52][CH2:53][CH:54]2[CH2:56][CH2:55]2)[CH:46]=[CH:45][C:26]=1[O:27][CH2:28][CH:29]([OH:44])[CH2:30]NCCNC([NH:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40]C=1)=O)#[N:24].BrBr.BrC1C=C(OCCOCC2CC2)C=CC=1O.C(=O)([O-])[O-].[K+].[K+].C(Br)C1C=CC=CC=1.C(OC1C=CC(OCCOCC2CC2)=CC=1Br)C1C=CC=CC=1>[Pd].CO.C(Cl)(Cl)Cl.CN(C)C=O.CC(C)=O.CCOCC>[NH:37]1[CH2:38][CH2:43][CH2:42][CH2:41][CH2:40]1.[O:44]1[CH2:30][CH:29]1[CH2:28][O:27][C:26]1[CH:45]=[CH:46][C:47]([O:49][CH2:50][CH2:51][O:52][CH2:53][CH:54]2[CH2:56][CH2:55]2)=[CH:48][C:25]=1[C:23]#[N:24]

Participants

15

Reactant 7

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 24408BromineHCID 19003845HCID 19003845, compoundHCID 19003849HCID 19003849, compoundHCID 19003850HCID 19003850, compoundHCID 54115755HCID 54115755, compound

Product 2

HCID 8082PiperidineHCID 19003839HCID 19003839, compound

Reagents, catalysts & solvents 6

HCID 23938PalladiumCatalystHCID 180AcetoneSolventHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

4-Benzyloxyphenel is reacted with 2-chloroethyl)cyclopropylmethyl)ether and the resultant 1-benzyloxy-4-(2-cyclopropylmethoxyethoxy)benzene is debenzylated by hydrogenation with palladium on charcoal. To a solution of the resultant 4-(2-cyclopropylmethoxyethoxy)phenol in methanol is added bromine dissolved in chloroform at 0° and the mixture stirred for 2 hours. After chromatography over silicagel, the resultant 2-bromo-4-(2-cyclopropylmethoxyethoxy)-phenol 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-cyclopropylmethoxyethoxy)benzene 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-cyclopropylmethoxyethoxy)benzonitrile is debenzylat-d over 10 % palladium on charcoal in methanol. The resultant 2-hydroxy-5(2-cyclopropylmethoxyethoxy)benzonitrile is reacted at 100° with epichlorhydrin and a catalytic amount of piperidine, and 2-(2,3-epoxypropoxy)-5-(2-cyclopropylmethoxyethoxy)benzonitrile is obtained.

Workup

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

Sources & evidence

ORD record
ord-698d7f1b22ad4ea9b8de2f72f4e7e24e
Source dataset
uspto-grants-1994_09
Patent number
US05347050

Reaction notes

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