Water → 2,3-Dihydro-1'-benzyl-6-chlorospiro[benzofuran-2,4'-piperidine]hydrochloride

HRID 261492Notes

Reaction equation

HRID 261492 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2F)([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CN(C)C=O.O>C1C=CC=CC=1.CCCCCC.CCOCC>[ClH:22].[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[O:14]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 127332221-Benzyl-4-(4-chloro-2-fluorobenzyl)-4-piperidinol

Product 1

HCID 705478832,3-Dihydro-1'-benzyl-6-chlorospiro[benzofuran-2,4'-piperidine]hydrochloride

Reagents, catalysts & solvents 3

HCID 241BenzeneSolvent2×HCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Procedure

A solution of 8.3 g of 1-benzyl-4-(4-chloro-2-fluorobenzyl)-4-piperidinol in 75 ml of benzene is added dropwise to a stirred suspension at ambient temperature of 1.5 g of sodium hydride (50% oil dispersion) in 100 ml of benzene. After total addition the reaction mixture is brought to reflux before adding 35 ml of dimethylformamide. Thereafter, the reaction mixture, sequentially, is refluxed for 15 minutes, cooled to ambient temperature, and diluted by the dropwise addition of 100 ml of water. The reaction mixture is poured into 1 liter of ice-water and extracted three times with ether. The combined ether extracts are successively washed with a saturated sodium chloride solution, dried and the ether is removed under reduced pressure, leaving an oil. The oil is boiled in hexane and the hexane is removed, leaving a yellow oil which solidifies upon standing. The oil is dissolved in ether where it is converted to its hydrogen chloride salt. The salt is recrystallized thrice from an ethyl alcohol-ether mixture to provide the product, 2,3-dihydro-1' -benzyl-6-chlorospiro[benzofuran-2,4'-piperidine]hydrochloride, mp 257°-259° C.

Workup

  1. additionAfter total addition the reaction mixture
  2. temperatureto reflux
  3. temperatureThereafter, the reaction mixture, sequentially, is refluxed for 15 minutes
  4. extractionextracted three times with ether
  5. washThe combined ether extracts are successively washed with a saturated sodium chloride solution
  6. customdried
  7. customthe ether is removed under reduced pressure
  8. customleaving an oil
  9. customthe hexane is removed
  10. customleaving a yellow oil which
  11. customThe salt is recrystallized thrice from an ethyl alcohol-ether mixture

Sources & evidence

ORD record
ord-0fdd477d7200498589e79a7c4975318e
Source dataset
uspto-grants-1979_08
Patent number
US04166119

Reaction notes

Loading…