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

HRID 1740104Notes

Reaction equation

HRID 1740104 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N:9]2[C:13]([CH2:14][CH3:15])=[C:12]([CH2:16][N:17]3[C@@H:26]([CH2:27][OH:28])[CH2:25][C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:18]3)[C:11]([CH2:29][CH3:30])=[N:10]2)=[C:4]([CH3:31])[CH:3]=1.[H-].[Na+].[CH2:34](I)[CH3:35]>O1CCCC1>[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N:9]2[C:13]([CH2:14][CH3:15])=[C:12]([CH2:16][N:17]3[C@@H:26]([CH2:27][O:28][CH2:34][CH3:35])[CH2:25][C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:18]3)[C:11]([CH2:29][CH3:30])=[N:10]2)=[C:4]([CH3:31])[CH:3]=1

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydride3×HCID 54272289(R)-{2-[1-(4-Bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-yl methyl]-1,2,3,4-tetrahydro-isoquinolin-3-yl}-methanol

Product 1

HCID 53638919(R)-2-[1-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-3-ethoxymethyl-1,2,3,4-tetrahydro-isoquinolineYield 141.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ambient temperature solution of (R)-{2-[1-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-1,2,3,4-tetrahydro-isoquinolin-3-yl }-methanol (0.45 g, 0.93 mmol) in anhydrous tetrahydrofuran (12 ml) was added sodium hydride (224 mg of 60% sodium hydride mineral oil dispersion; 5.6 mmol of sodium hydride was added. After stirring for 5 minutes, ethyl iodide (0.37 ml, 4.7 mmol) was added all at once. The reaction mixture was then stirred for 21 hours. The solvent was removed in vacuo, and the remaining residue was extracted with ethyl acetate/water (10 ml of each). The aqueous phase was separated, and then extracted twice with equal volumes of fresh ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to afford a yellow oil (0.67 g). Flash chromatography (silica gel, 40 micron mesh; elution with ethyl acetate/hexane =1:6 in volume) afforded the title compound as a light yellow oil (332 mg).

Workup

  1. stirringThe reaction mixture was then stirred for 21 hours
  2. customThe solvent was removed in vacuo
  3. extractionthe remaining residue was extracted with ethyl acetate/water (10 ml of each)
  4. customThe aqueous phase was separated
  5. extractionextracted twice with equal volumes of fresh ethyl acetate
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-29704d8459b44dcaace328bcfd3d05c9
Source dataset
uspto-grants-1999_10
Patent number
US05968944

Reaction notes

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