Methyl iodide → 6,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline

HRID 48249Notes

Reaction equation

HRID 48249 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N+:7](C)([CH3:13])[CH2:6][CH:5]2[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.FC(F)(F)C([O-])=O.CI>Cl.CC(C)=O.C(N(C(C)C)CC)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 3

HCID 6328Methyl iodide2×HCID 84468TrifluoroacetateHCID 121125146,8-Dichloro-2,2-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolinium

Product 1

HCID 223868076,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 313Hydrochloric AcidSolventHCID 81531DiisopropylethylamineSolvent

Procedure

6,8-Dichloro-2,2-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolinium, trifluoroacetate; Intermediate 4 (100 mg) was dissolved in the form of its hydrochloride in acetone (1 ml) in the presence of diisopropylethylamine (58 μl). Methyl iodide (38 μl) was then added dropwise with stirring. The mixture was then stirred at room temperature for two hours and subsequently left to stand for 62 h. Since the reaction was still not complete, further methyl iodide (38 μl) was added and the mixture was heated to reflux. After two hours, the reaction mixture was cooled and then concentrated to dryness in a rotary evaporator. The residue was purified by preparative HPLC on RP-18 with acetonitrile/water (0.05% TFA), and the pure fractions were combined. The acetonitrile was stripped off and then the aqueous residue was freeze dried. 132 mg of the desired product were obtained as a solid. (Rt=4.22 min (method A); MS (Cl+): 306.0).

Workup

  1. stirringThe mixture was then stirred at room temperature for two hours
  2. waitsubsequently left
  3. temperaturethe mixture was heated to reflux
  4. waitAfter two hours
  5. temperaturethe reaction mixture was cooled
  6. concentrationconcentrated to dryness in a rotary evaporator
  7. customThe residue was purified by preparative HPLC on RP-18 with acetonitrile/water (0.05% TFA)
  8. customdried

Sources & evidence

ORD record
ord-10a7641c12c744048014d48f2b6c6477
Source dataset
uspto-grants-2004_03
Patent number
US06703405B2

Reaction notes

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