Benzyl Bromide → Piperidine

HRID 2295529Notes

Reaction equation

HRID 2295529 reaction equation
C(OC1C=CC(O)=CC=1)C1C=CC=CC=1.C(OC1C=CC(OCCOCC2CC2)=CC=1)C1C=CC=CC=1.[C:38]([C:40]1[CH:63]=[C:62]([O:64][CH2:65][CH2:66][O:67][CH2:68][CH:69]2[CH2:71][CH2:70]2)[CH:61]=[CH:60][C:41]=1[O:42][CH2:43][CH:44]([OH:59])[CH2:45]NCCNC([NH:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55]C=1)=O)#[N:39].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:52]1[CH2:53][CH2:58][CH2:57][CH2:56][CH2:55]1.[O:59]1[CH2:45][CH:44]1[CH2:43][O:42][C:41]1[CH:60]=[CH:61][C:62]([O:64][CH2:65][CH2:66][O:67][CH2:68][CH:69]2[CH2:71][CH2:70]2)=[CH:63][C:40]=1[C:38]#[N:39]

Participants

16

Reactant 8

HCID 7498Benzyl BromideHCID 7638MonobenzoneHCID 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-Benzyloxyphenol 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 debenzylated 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-dfb87eed542a4a03960ad5e1539275a4
Source dataset
uspto-grants-1984_01
Patent number
US04425362

Reaction notes

Loading…