Phenethyl bromide → HCID 21465089, compound

HRID 1939886Notes

Reaction equation

HRID 1939886 reaction equation
[C:1]1([CH2:7][CH2:8]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O=[C:11]1[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]1.[NH4+].[Cl-]>C1COCC1>[C:1]1([CH2:7][CH2:8][C:11]2[CH2:16][CH2:15][CH:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:1]1([CH2:7][CH2:8][C:11]23[CH2:12][CH2:13][CH:14]([CH2:15][CH2:16]2)[C:17](=[O:18])[O:19]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 7666Phenethyl bromideHCID 25517Ammonium ChlorideHCID 317638Ethyl 4-oxocyclohexanecarboxylate

Product 2

HCID 21465089HCID 21465089, compoundHCID 21465100HCID 21465100, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Slowly add 2-phenylethyl bromide (2.6 g) to a slurry of Mg (0.37 g) in THF (50 mL) and heat at reflux for 4 h. Cool the solution to ambient temperature and add to a solution of ethyl 4-oxo-cyclo-hexanecarboxylate (2.4 g) in THF (50 mL). After 2 h, pour the reaction mixture into a half-saturated solution of NH4Cl and extract with EtOAc. Partially purify the product on a silica gel column, eluting with EtOAc. Dissolve the product in toluene (100 mL), treat with p-TsOH and heat at reflux overnight with azeotropic removal of water. Cool the reaction mixture, wash with saturated NaHCO3 solution and concentrate. Purify the crude product on a silica gel column, eluting with CH2Cl2 to obtain ethyl 4-(2-phenylethyl)-cyclohex-3-enecarboxylate (0.45 g) and 1-(2-phenyl-ethyl)-2-oxabicyclo[2.2.2]octan-3-one (0.71 g). Dissolve 1-(2-phenyl-ethyl)-2-oxabicyclo[2.2.2]octan-3-one in EtOH, treat with conc.HCl (catalytic) and heat at reflux overnight. Dilute the reaction mixture with water and extract with EtOAc. Concentrate the organic layer to obtain additional ethyl 4-(2-phenylethyl)-cyclohex-3-enecarboxylate (0.88 g).

Workup

  1. temperatureat reflux for 4 h
  2. extractionextract with EtOAc
  3. customPartially purify the product on a silica gel column
  4. washeluting with EtOAc
  5. dissolutionDissolve the product in toluene (100 mL)
  6. additiontreat with p-TsOH
  7. temperatureheat
  8. temperatureat reflux overnight with azeotropic removal of water
  9. temperatureCool the reaction mixture
  10. washwash with saturated NaHCO3 solution
  11. concentrationconcentrate
  12. customPurify the crude product on a silica gel column
  13. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-9e71d902d0b14edfabcb0b4bb007c360
Source dataset
uspto-grants-1997_12
Patent number
US05698548

Reaction notes

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