Methyl iodide → HCID 68829536, compound

HRID 1986485Notes

Reaction equation

HRID 1986485 reaction equation
[C:1]([C:3]1[C:4]([CH2:29][CH:30]([CH3:32])[CH3:31])=[N:5][C:6]2[C:11]([C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)=[CH:10][C:9]([NH:20][CH2:21][C:22]([O:24][C:25](C)(C)C)=[O:23])=[CH:8][CH:7]=2)#[N:2].FC(F)(F)C(O)=O.CI.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[C:1]([C:3]1[C:4]([CH2:29][CH:30]([CH3:32])[CH3:31])=[N:5][C:6]2[C:11]([C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([CH3:19])=[CH:17][CH:18]=1)=[CH:10][C:9]([NH:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:8][CH:7]=2)#[N:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 68832140HCID 68832140, compound

Product 1

HCID 68829536HCID 68829536, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl N-[3-cyano-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]glycinate (3.0 g, 7.0 mmol) in tetrahydrofuran (10 ml) was added trifluoroacetic acid (820 ml), and the mixture was stirred at room temperature for 6 hrs. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl-acetate and water. The aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue (3.0 g) was dissolved in N,N-dimethylformamide (10 ml). Thereto were added methyl iodide (1.5 g, 5.3 mmol) and potassium carbonate (0.73 g, 5.3 mmol) and the mixture was stirred at room temperature for 2 days. The reaction mixture was partitioned between ethyl acetate and water, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed successively with 0.1 M aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give methyl N-[3-cyano-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]glycinate (1.6 g, yield 79%) as a pale-yellow powder. Subsequently, methyl N-[3-(aminomethyl)-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]glycinate (1.0 g, yield 62%, pale-yellow powder) was synthesized by a method similar to the method shown in Example 25(2).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was partitioned between ethyl-acetate and water
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. dissolutionthe residue (3.0 g) was dissolved in N,N-dimethylformamide (10 ml)
  8. stirringthe mixture was stirred at room temperature for 2 days
  9. customThe reaction mixture was partitioned between ethyl acetate and water
  10. extractionthe aqueous layer was extracted with ethyl acetate
  11. washwashed successively with 0.1 M aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-29da7412d23b4783bdc7c21aa393c11d
Source dataset
uspto-grants-2009_06
Patent number
US07547710B2

Reaction notes

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