Tetrahydrofuran → HCID 12213082, compound

HRID 1077318Notes

Reaction equation

HRID 1077318 reaction equation
[CH3:1][O:2][CH:3]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1Br.O1CCCC1.C([Li])CCC.[CH3:27][N:28]1[CH2:33][CH2:32]C(=O)[CH2:30][CH2:29]1>CCCCCC.O>[CH3:27][N:28]1[CH2:33][CH2:32][C:1]2([C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[O:2]2)[CH2:30][CH2:29]1

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 740491-Methyl-4-piperidoneHCID 12319472HCID 12319472, compoundHCID 178418339Butyllithium

Product 1

HCID 12213082HCID 12213082, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8058HexaneSolvent2×

Procedure

To a cold (-60°) stirred solution of 2-bromobenzhydryl methyl ether in 38 ml. of tetrahydrofuran and 14 ml. of hexane is slowly added 53 ml. of 2.1 M n-butyllithium in hexane. After 2 hours, a solution of 10.7 g. of 1-methyl-4-piperidone in 15 ml. of tetrahydrofuran is added dropwise, and the suspension is stirred at -60° for 3 hours and at room temperature for 15 hours. Ice and water are added and the mixture is extracted with chloroform. The chloroform solution is dried over sodium sulfate and concentrated to a mixture of 4-hydroxy-4-(α-methoxy-α-phenyl-2-tolyl)-1-methylpiperidine and benzhydrol methyl ether. This oil is heated under reflux for 30 minutes if 240 ml. of acetic acid containing 60 ml. of hydrochloric acid. Dilution with water and addition of excess sodium hydroxide effects precipitation of a solid. Recrystallization from hexane provides 1,3-dihydro-1'-methyl-3-phenylspiro[isobenzofuran-1,4'-piperidine], m.p. 123°-124°.

Workup

  1. extractionthe mixture is extracted with chloroform
  2. dry with materialThe chloroform solution is dried over sodium sulfate
  3. concentrationconcentrated to a mixture of 4-hydroxy-4-(α-methoxy-α-phenyl-2-tolyl)-1-methylpiperidine and benzhydrol methyl ether
  4. temperatureThis oil is heated
  5. temperatureunder reflux for 30 minutes if 240 ml
  6. additionDilution with water and addition of excess sodium hydroxide
  7. customprecipitation of a solid
  8. customRecrystallization from hexane

Sources & evidence

ORD record
ord-ab1021a9041f4ffca25bcf547a0e0cb0
Source dataset
uspto-grants-1976_05
Patent number
US03959475

Reaction notes

Loading…