Sodium hydride → 6-Chloro-2'-methylspiro[benzofuran-2(3H),4'(2'H)-isoquinoline] hydrochloride

HRID 648095Notes

Reaction equation

HRID 648095 reaction equation
[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][C:7]2([OH:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:10][N:9]([CH3:17])[CH2:8]2)=[C:4](F)[CH:3]=1.[H-].[Na+]>C1(C)C=CC=CC=1.CN(C)C=O.O.CCOCC>[ClH:1].[Cl:1][C:2]1[CH:20]=[CH:19][C:5]2[CH2:6][C:7]3([O:18][C:4]=2[CH:3]=1)[C:16]1[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH2:10][N:9]([CH3:17])[CH2:8]3

Participants

7

Reactant 2

HCID 24758Sodium hydrideHCID 15917420HCID 15917420, compound

Product 1

HCID 159174396-Chloro-2'-methylspiro[benzofuran-2(3H),4'(2'H)-isoquinoline] hydrochlorideYield 129.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(4-chloro-2-fluorobenzyl)-2-methyl-1,2,3,4-tetrahydro-4-isoquinolinol (10.0 g) in toluene (65 ml) and dimethylformamide (10 ml) is added dropwise to a suspension of sodium hydride (50%, 3.2 g), previously washed with hexane, in toluene (65 ml). After the addition is complete, the mixture is brought to reflux and dimethylformamide (35 ml) is slowly added dropwise. The reaction mixture is heated under reflux for four hours. Removal of the solvents yields an oil which is stirred in water (500 ml) and extracted with chloroform. The combined organic extracts are washed with water, saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After filtering, removal of the solvent yields an oil which is dissolved in ether and converted to the product hydrochloride salt. The salt is recrystallized from ethyl acetate/methanol to yield the product as a white solid (6.8 g, 60%), mp 196°-199°. An analytical sample is twice recrystallized to yield a white solid, mp 200.5°-202° (dec.).

Workup

  1. washpreviously washed with hexane, in toluene (65 ml)
  2. additionAfter the addition
  3. temperatureto reflux
  4. additiondimethylformamide (35 ml) is slowly added dropwise
  5. temperatureThe reaction mixture is heated
  6. temperatureunder reflux for four hours
  7. customRemoval of the solvents
  8. customyields an oil which
  9. extractionextracted with chloroform
  10. washThe combined organic extracts are washed with water, saturated sodium chloride solution
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationAfter filtering
  13. customremoval of the solvent
  14. customyields an oil which
  15. customThe salt is recrystallized from ethyl acetate/methanol

Sources & evidence

ORD record
ord-e360ef25caf340838a1afffefbe92313
Source dataset
uspto-grants-1983_10
Patent number
US04410699

Reaction notes

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