Sodium hydride → 6-[(2RS,4SR)-2-(4-chlorophenyl)-2-bromomethyl-1,3-dioxolan-4-ylmethyloxy]-2-(4-phenylbenzyl)-1,2,3,4-tetrahydroisoquinoline

HRID 2413488Notes

Reaction equation

HRID 2413488 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH2:10][N:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=1)[CH2:8][CH2:7]2.CS(O[CH2:32][CH:33]1[CH2:37][O:36][C:35]([C:40]2[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][CH:41]=2)([CH2:38][Br:39])[O:34]1)(=O)=O>CN(C)C=O>[Cl:46][C:43]1[CH:42]=[CH:41][C:40]([C:35]2([CH2:38][Br:39])[O:34][CH:33]([CH2:32][O:3][C:4]3[CH:5]=[C:6]4[C:11](=[CH:12][CH:13]=3)[CH2:10][N:9]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[CH:17][CH:16]=3)[CH2:8][CH2:7]4)[CH2:37][O:36]2)=[CH:45][CH:44]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 133618036-Hydroxy-2-(4-phenylbenzyl)-1,2,3,4-tetrahydroisoquinolineHCID 155764512-Bromomethyl-2-(4-chlorophenyl)-1,3-dioxolan-4-ylmethyl methanesulfonate

Product 1

HCID 201558156-[(2RS,4SR)-2-(4-chlorophenyl)-2-bromomethyl-1,3-dioxolan-4-ylmethyloxy]-2-(4-phenylbenzyl)-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.1 g of sodium hydride (50% suspension in oil) are added in portions, with cooling, to a solution of 6.3 g of 6-hydroxy-2-(4-phenylbenzyl)-1,2,3,4-tetrahydroisoquinoline in 100 ml of dry dimethylformamide. The mixture is stirred at 50° for 1 hour and then 7.7 g of (2RS,4SR)-2-(4-chlorophenyl)-2-bromomethyl-1,3-dioxolan-4-ylmethyl methanesulfonate (preparation as in European Offenlegungsschrift No. 0,050,298) are added. The mixture is stirred at 80° C. for 5 hours and cooled, the solvent is removed under oil pump vacuum, and the residue is taken up with a mixture of water and methylene chloride. After washing twice with water and drying over magnesium sulfate, the solution is evaporated in a rotary evaporator, and the residue is chromatographed on silica gel with a mixture of methylene chloride and ethyl acetate in the ratio 3:1. 7.0 g of a highly viscous oil (58% of theory) are obtained.

Workup

  1. stirringThe mixture is stirred at 80° C. for 5 hours
  2. temperaturecooled
  3. customthe solvent is removed under oil pump vacuum
  4. additionthe residue is taken up with a mixture of water and methylene chloride
  5. washAfter washing twice with water
  6. dry with materialdrying over magnesium sulfate
  7. customthe solution is evaporated in a rotary evaporator
  8. customthe residue is chromatographed on silica gel with a mixture of methylene chloride and ethyl acetate in the ratio 3:1
  9. custom7.0 g of a highly viscous oil (58% of theory) are obtained

Sources & evidence

ORD record
ord-a2f02b03a2664370b8cb64cc54dd4564
Source dataset
uspto-grants-1988_01
Patent number
US04717724

Reaction notes

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