Water → 4-(p-Chlorophenoxy)-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride

HRID 1583379Notes

Reaction equation

HRID 1583379 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+].[Cl:15][C:16]1[CH:21]=[CH:20][C:19](F)=[CH:18][CH:17]=1.O>CN(C=O)C>[ClH:15].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([O:12][CH:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH2:3][N:2]([CH3:1])[CH2:11]2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 9604Benzene, 1-chloro-4-fluoro-HCID 24758Sodium hydrideHCID 125230552-Methyl-1,2,3,4-tetrahydro-4-isoquinolinol

Product 1

HCID 131171004-(p-Chlorophenoxy)-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrochlorideYield 43.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

A solution of 1,2,3,4-tetrahydro-2-methyl-4-isoquinolinol (3.3 g, 0.020 mole) in dry DMF is added dropwise under nitrogen to a suspension of sodium hydride 50% (98%) (1.6 g, 0.033 mole), previously washed with hexane, in 40 ml dry DMF, at 65° C. After the evolution of gas ceases, a solution of p-chlorofluorobenzene (3.6 g, 0.028 mole) in 15 ml dry DMF is added slowly, and the resulting mixture is allowed to stir at 75° C. for 16 hours. After cooling to room temperature the solution is poured into water (110 ml), extracted with chloroform, the chloroform phase is washed twice with water, dried (saturated NaCl, anhydrous MgSO4) and removed via reduced pressure to yield an oil which is purified by dry column chromatography, over silica gel using ethyl acetate as the eluent. The desired product is crystallized from ether as the hydrochloride salt, yielding 1.9 g (31%) of a solid of 4-(p-chlorophenoxy)-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride, d @ 92° C.

Workup

  1. washpreviously washed with hexane, in 40 ml dry DMF, at 65° C
  2. temperatureAfter cooling to room temperature the solution
  3. extractionextracted with chloroform
  4. washthe chloroform phase is washed twice with water
  5. dry with materialdried (saturated NaCl, anhydrous MgSO4)
  6. customremoved via reduced pressure
  7. customto yield an oil which
  8. customis purified
  9. customby dry column chromatography
  10. customThe desired product is crystallized from ether as the hydrochloride salt

Sources & evidence

ORD record
ord-724bed00e6b44e5493dfb8f399ef83fd
Source dataset
uspto-grants-1985_11
Patent number
US04551474

Reaction notes

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