Iodoethane → (R)-2-[3,5-Diethyl-1-(4-ethyl-2,6-dimethylphenyl)-1H-pyrazol-4-ylmethyl]-3-ethoxymethyl-1,2,3,4-tetrahydro-isoquinoline

HRID 1740107Notes

Reaction equation

HRID 1740107 reaction equation
[CH2:1]([Li])[CH2:2]CC.Br[C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([N:14]2[C:18]([CH2:19][CH3:20])=[C:17]([CH2:21][N:22]3[C@@H:31]([CH2:32][O:33][CH2:34][CH3:35])[CH2:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:23]3)[C:16]([CH2:36][CH3:37])=[N:15]2)=[C:9]([CH3:38])[CH:8]=1.C(I)C>O1CCCC1>[CH2:36]([C:16]1[C:17]([CH2:21][N:22]2[C@@H:31]([CH2:32][O:33][CH2:34][CH3:35])[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:23]2)=[C:18]([CH2:19][CH3:20])[N:14]([C:10]2[C:11]([CH3:13])=[CH:12][C:7]([CH2:1][CH3:2])=[CH:8][C:9]=2[CH3:38])[N:15]=1)[CH3:37]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 53638919(R)-2-[1-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-3-ethoxymethyl-1,2,3,4-tetrahydro-isoquinolineHCID 178418339Butyllithium

Product 1

HCID 67553167(R)-2-[3,5-Diethyl-1-(4-ethyl-2,6-dimethylphenyl)-1H-pyrazol-4-ylmethyl]-3-ethoxymethyl-1,2,3,4-tetrahydro-isoquinolineYield 71.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of n-butyl lithium (2.5 M hexane solution; 0.062 ml, 0.16 mmol) chilled to -78° C., a solution of (R)-2-[1-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-3-ethoxymethyl-1,2,3,4-tetrahydro-isoquinoline (72 mg, 0.14 mmol) in anhydrous tetrahydrofuran (0.2 ml) was added dropwise. After stirring at -78° C. for 10 minutes, anhydrous ethyl iodide (0.056 ml, 0.70 mmol) was added. The resulting mixture was warmed to ambient temperature and stirred for 1 hour. The reaction was quenched by addition of aqueous ammonium chloride (1 ml), then extracted with ethyl acetate/water (5 ml of each). The separated organic extract was washed with an equal volume solution of aqueous ammonium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo to afford a yellow oil (46 mg). Flash chromatography (silica gel, 40 micron mesh; elution with ethyl actate/hexane=1:5 in volume) afforded the title compound (10 mg) as a light yellow oil.

Workup

  1. temperatureThe resulting mixture was warmed to ambient temperature
  2. stirringstirred for 1 hour
  3. customThe reaction was quenched by addition of aqueous ammonium chloride (1 ml)
  4. extractionextracted with ethyl acetate/water (5 ml of each)
  5. extractionThe separated organic extract
  6. washwas washed with an equal volume solution of aqueous ammonium chloride
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-47312e7f01cd48978ff4605c2fe6ca28
Source dataset
uspto-grants-1999_10
Patent number
US05968944

Reaction notes

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