Fluorobenzene → 2-Methyl-4-phenoxy-1,2,3,4-tetrahydroisoquinoline

HRID 1583380Notes

Reaction equation

HRID 1583380 reaction equation
[CH3:1][N:2]1[CH2:11][CH:10]([OH:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1.[H-].[Na+].F[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:11][CH:10]([O:12][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1

Participants

5

Reactant 3

HCID 10008FluorobenzeneHCID 24758Sodium hydrideHCID 125230552-Methyl-1,2,3,4-tetrahydro-4-isoquinolinol

Product 1

HCID 133401602-Methyl-4-phenoxy-1,2,3,4-tetrahydroisoquinolineYield 65.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
95 °C

Procedure

A solution of 2-methyl-1,2,3,4-tetrahydro-4-isoquinolinol (6.0 g, 0.037 mole) in 30 ml dry DMF is added dropwise under nitrogen to a suspension of sodium hydride 50% (98%) (2.2 g, 0.044 mole), previously washed with hexane, in 50 ml dry DMF. After one hour the mixture is slowly warmed to 75° C. at which time fluorobenzene (7.1 g. 0.074 mole) in 30 ml dry DMF is added dropwise. The reaction mixture is stirred at 95° C. for four hours then at 75° C. for about 16 hours. Most of the solvent is removed under reduced pressure and the resultant mixture is stirred in 500 ml water then extracted with chloroform. The combined organic extracts are washed twice with water and then dried (saturated NaCl, anhydrous MgSO4). Removal of solvent yields 5.8 g (65%) of an oil which is purified by dry column chromatography over silica gel using ethyl acetate as the eluent. The desired product is extracted with chloroform to yield 1.5 g (17%) of an oil of 2-methyl-4-phenoxy-1,2,3,4-tetrahydroisoquinoline.

Workup

  1. washpreviously washed with hexane, in 50 ml dry DMF
  2. additionis added dropwise
  3. waitat 75° C. for about 16 hours
  4. customMost of the solvent is removed under reduced pressure
  5. stirringthe resultant mixture is stirred in 500 ml water
  6. extractionthen extracted with chloroform
  7. washThe combined organic extracts are washed twice with water
  8. dry with materialdried (saturated NaCl, anhydrous MgSO4)
  9. customRemoval of solvent

Sources & evidence

ORD record
ord-4c5b7ba0348941e8b2bef8f195cdb6fc
Source dataset
uspto-grants-1985_11
Patent number
US04551474

Reaction notes

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