Potassium Iodide → RS-17053

HRID 1648393

Reaction equation

HRID 1648393 reaction equation
CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH2:16][CH:17]1[CH2:19][CH2:18]1)(=O)=O.[I-].[K+].[Cl:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][CH:27]=[C:26]2[CH2:32][C:33]([NH2:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[ClH:22].[Cl:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][CH:27]=[C:26]2[CH2:32][C:33]([NH:36][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH2:16][CH:17]1[CH2:18][CH2:19]1)([CH3:34])[CH3:35]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 132605-Chloro-alpha,alpha-dimethyl-1H-indole-3-ethanamineHCID 152896252-[2-(Cyclopropylmethyloxy)phenoxy]ethyl methanesulfonate

Product 1

HCID 9824953RS-17053Yield 160.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
120 °C

Procedure

2-[2-(cyclopropylmethyloxy)phenoxy]ethyl methanesulfonate (8.0 g, 28.0 mmol) and potassium iodide (4.65 g, 28.0 mmol) were combined in DMF and the mixture was stirred at 120° C. for 15 minutes. [2-(5-Chloro-1H-indol-3-yl)-1,1-dimethyl-ethyl]amine (4.77 g, 21.7 mmol) and potassium carbonate (5.8 g, 42.0 mmol) were added to the mixture, which was then diluted with DMF (≈50 mL) and stirred at 130°-135° C. and under nitrogen for 2 hours. The mixture was cooled, poured into water (≈800 mL), and then extracted into ether. The organic phase was separated, washed once with water and then brine, dried over magnesium sulfate, and evaporated. The residue was dissolved in ethyl acetate, 5% hydrochloric acid in methanol was added, and the solution was evaporated. The residue was dissolved in ethyl acetate and a small amount of methanol and the solution was evaporated. The residue was again dissolved in ethyl acetate and methanol and the solution was evaporated. Filtration gave [2-(5-chloro-1H-indol-3-yl)-1,1-dimethylethyl][2-(2-cyclopropylmethyloxyphenoxy)ethyl]amine hydrochloride (7.8 g, 17.4 mmol), m.p. 199°-201° C.

Workup

  1. stirringstirred at 130°-135° C. and under nitrogen for 2 hours
  2. temperatureThe mixture was cooled
  3. extractionextracted into ether
  4. customThe organic phase was separated
  5. washwashed once with water
  6. dry with materialbrine, dried over magnesium sulfate
  7. customevaporated
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. addition5% hydrochloric acid in methanol was added
  10. customthe solution was evaporated
  11. dissolutionThe residue was dissolved in ethyl acetate
  12. customa small amount of methanol and the solution was evaporated
  13. dissolutionThe residue was again dissolved in ethyl acetate
  14. custommethanol and the solution was evaporated
  15. filtrationFiltration

Sources & evidence

ORD record
ord-bf2b23efd9df45339a726ab1d0841803
Source dataset
uspto-grants-1995_07
Patent number
US05436264

Linked notes

Loading…