Hydrochloric Acid → 1'-benzyl-6-ethylspiro[isobenzofuran-1(3H),4'-piperidine]-3-one hydrochloride

HRID 2268069Notes

Reaction equation

HRID 2268069 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10]CC(C)(C)N=2)=[CH:5][CH:4]=1)[CH3:2].CCCCCC.C([Li])CCC.[CH2:27]([N:34]1[CH2:39][CH2:38][C:37](=[O:40])[CH2:36][CH2:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[ClH:41].[OH-].[Na+]>O1CCCC1>[ClH:41].[CH2:27]([N:34]1[CH2:39][CH2:38][C:37]2([C:7]3[C:6](=[CH:5][CH:4]=[C:3]([CH2:1][CH3:2])[CH:8]=3)[C:9](=[O:10])[O:40]2)[CH2:36][CH2:35]1)[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 128725592-(4-Ethylphenyl)-4,4-dimethyl-2-oxazolineHCID 178418244HCID 178418244, compound

Product 1

HCID 226607251'-benzyl-6-ethylspiro[isobenzofuran-1(3H),4'-piperidine]-3-one hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere, a solution of 2-(4-ethylphenyl)-4,4-dimethyl-2-oxazoline (1.15 g) in anhydrous tetrahydrofuran (100 mL) was cooled to −78° C. To this solution was added 1.5 M butyl lithium hexane solution (4.53 mL). After being stirred for 1 hour, 1-benzyl-4-piperidone (1.05 mL) was added dropwise. After the reaction temperature was allowed to rise up to room temperature, 2N hydrochloric acid was added to the reaction mixture to make the mixture acidic. The whole was refluxed for 2 hours. After cooling, sodium hydroxide aqueous solution was added to make the reaction mixture basic. The mixture was extracted with ethyl ether. The organic layer was washed with saturated saline solution and then dried over anhydrous Na2SO4. The concentration of the organic solvent left a residue, which was purified by column chromatography on silica gel (hexane/ethyl acetate/=3/2) to give the subject compound (409 mg).

Workup

  1. customto rise up to room temperature
  2. temperatureThe whole was refluxed for 2 hours
  3. temperatureAfter cooling
  4. extractionThe mixture was extracted with ethyl ether
  5. washThe organic layer was washed with saturated saline solution
  6. dry with materialdried over anhydrous Na2SO4
  7. waitThe concentration of the organic solvent left a residue, which
  8. customwas purified by column chromatography on silica gel (hexane/ethyl acetate/=3/2)

Sources & evidence

ORD record
ord-b6044a81c2744ed8a6788088c3bc428b
Source dataset
uspto-grants-2001_12
Patent number
US06326375B1

Reaction notes

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