Methyl iodide → isopropyl 2-(3-((6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)(methyl)amino)phenoxy)acetate

HRID 1051099Notes

Reaction equation

HRID 1051099 reaction equation
[CH3:1]I.[H-].[Na+].[F:5][C:6]1[CH:7]=[C:8]([C:12]2[CH:20]=[C:19]3[C:15]([CH2:16][CH2:17][CH:18]3[NH:21][C:22]3[CH:23]=[C:24]([CH:33]=[CH:34][CH:35]=3)[O:25][CH2:26][C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28])=[CH:14][CH:13]=2)[CH:9]=[CH:10][CH:11]=1>CN(C)C=O>[F:5][C:6]1[CH:7]=[C:8]([C:12]2[CH:20]=[C:19]3[C:15]([CH2:16][CH2:17][CH:18]3[N:21]([CH3:1])[C:22]3[CH:23]=[C:24]([CH:33]=[CH:34][CH:35]=3)[O:25][CH2:26][C:27]([O:29][CH:30]([CH3:31])[CH3:32])=[O:28])=[CH:14][CH:13]=2)[CH:9]=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 118161547isopropyl 2-(3-((6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)amino)phenoxy)acetate

Product 1

HCID 118161542isopropyl 2-(3-((6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)(methyl)amino)phenoxy)acetateYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Methyl iodide (17 mg, 0.122 mmol) and sodium hydride (60% dispersion of mineral oil, 1.1 mg, 0.045 mmol) were added to a solution of isopropyl 2-(3-((6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)amino)phenoxy)acetate (17 mg, 0.041 mmol) and dimethylformamide (2 mL) in a 50 mL round bottom flask at room temperature. The mixture was then heated to 50° C. and allowed to stir overnight. The solution was quenched with saturated ammonium chloride (25 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with brine (1×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The resulting crude residue was purified by preparative TLC (1000 mm thickness, 30% ethyl acetate/hexanes) to afford 12 mg (68%) of isopropyl 2-(3-((6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)(methyl)amino)phenoxy)acetate.

Workup

  1. customThe solution was quenched with saturated ammonium chloride (25 mL)
  2. extractionextracted with ethyl acetate (100 mL)
  3. washThe organic layer was washed with brine (1×100 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting crude residue was purified by preparative TLC (1000 mm thickness, 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ef871945e4c74dfead6703e948324fc3
Source dataset
uspto-grants-2016_07
Patent number
US09388153B2

Reaction notes

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