Phosphorus oxychloride → 2-(3,4-Dichlorophenyl)-1-(4-hydroxybenzyl)-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinoline

HRID 1180171Notes

Reaction equation

HRID 1180171 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:23]=2)[C:10](=O)[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].P(Cl)(Cl)(Cl)=O.[BH4-].[Na+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:20][CH2:21][C:22]3[C:27](=[CH:26][CH:25]=[C:24]([O:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH:23]=3)[CH:10]2[CH2:11][C:12]2[CH:13]=[CH:14][C:15]([OH:18])=[CH:16][CH:17]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 4311764Sodium borohydrideHCID 23440903N-(3,4-Dichlorophenyl)-2-(4-hydroxyphenyl)-N-(2-[3-(phenylmethoxy)phenyl]ethyl}acetamide

Product 1

HCID 234407442-(3,4-Dichlorophenyl)-1-(4-hydroxybenzyl)-6-(phenylmethoxy)-1,2,3,4-tetrahydroisoquinolineYield 6.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-(3,4-dichlorophenyl)-2-(4-hydroxyphenyl)-N-{2-[3-(phenylmethoxy)phenyl]ethyl}acetamide (7.6 g, 0.015 mol) in acetonitrile (30 ml) was added phosphorus oxychloride (4.19 ml, 0.045 mol). The reaction was allowed to reflux at 80° C. for 6 hours. Solvent was removed and the reaction was placed on ice. To the flask was added ice and water. The reaction was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered, concentrated, and then dissolved in methanol. To the flask was added small aliquots of sodium borohydride (1.02 g, 0.027 mol). The reaction was allowed to stir overnight. The solvent was removed and the reaction was diluted with dichloromethane and water. The organic layer was separated and the aqueous layer was extracted with additional dichloromethane. The organic layers were combined, washed with brine, dried over MgSO4, filtered and concentrated to provide the title compound (0.5 g, 6.8% yield): ES-MS (m/z) 490 [M+H]+.

Workup

  1. customSolvent was removed
  2. additionTo the flask was added ice and water
  3. extractionThe reaction was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutiondissolved in methanol
  9. customThe solvent was removed
  10. additionthe reaction was diluted with dichloromethane and water
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was extracted with additional dichloromethane
  13. washwashed with brine
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-c2805171ad5e4e778d7f591dd519eeb0
Source dataset
uspto-grants-2007_10
Patent number
US07279489B2

Reaction notes

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