Hydrogen Peroxide → Silodosin

HRID 1173783Notes

Reaction equation

HRID 1173783 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([CH2:16][C@H:17]([NH:19][CH2:20][CH2:21][O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:29][CH2:30][C:31]([F:34])([F:33])[F:32])[CH3:18])=[CH:11][C:12]=2[C:14]#[N:15])[CH2:7][CH2:6]1.[OH-].[Na+].OO.S([O-])([O-])=[O:40].[Na+].[Na+]>CS(C)=O.O>[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([CH2:16][C@H:17]([NH:19][CH2:20][CH2:21][O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[O:29][CH2:30][C:31]([F:34])([F:32])[F:33])[CH3:18])=[CH:11][C:12]=2[C:14]([NH2:15])=[O:40])[CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 24437Sodium Sulfite2×HCID 115330471H-Indole-7-carbonitrile, 2,3-dihydro-1-(3-hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]aMino]propyl]-

Product 1

HCID 5312125Silodosin

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
22.5 °C

Procedure

1-(3-Hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carbonitrile(6.00 g) was dissolved in dimethylsulfoxide (75 mL), and to the solution was added 5 mol/L aqueous sodium hydroxide solution(4.50 mL). To the reaction mixture, 30% hydrogen peroxide (2.63 mL) was added little by little at not more than 25° C. The reaction mixture was stirred at 20 to 25° C. for 5 hours. To the reaction mixture, an aqueous sodium sulfite solution of sodium sulfite (2.1 g) dissolved in water (150 mL) was added carefully. The reaction mixture was extracted twice with ethyl acetate (50 mL). The combined ethyl acetate layer was extracted twice with 2 mol/L hydrochloric acid. The aqueous hydrochloric acid solution extracted was neutralized with sodium bicarbonate, and extracted twice with ethyl acetate (50 mL). The combined ethyl acetate layer was washed with a saturated aqueous sodium bicarbonate solution and brine and dried over anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate. The solution was cooled to give 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]-ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide (4.49 g).

Workup

  1. additionwas added carefully
  2. extractionThe reaction mixture was extracted twice with ethyl acetate (50 mL)
  3. extractionThe combined ethyl acetate layer was extracted twice with 2 mol/L hydrochloric acid
  4. extractionThe aqueous hydrochloric acid solution extracted
  5. extractionextracted twice with ethyl acetate (50 mL)
  6. washThe combined ethyl acetate layer was washed with a saturated aqueous sodium bicarbonate solution and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. dissolutionthe residue was dissolved in ethyl acetate
  10. temperatureThe solution was cooled

Sources & evidence

ORD record
ord-473b0ad300de4a20bd0e3db1fb3e8453
Source dataset
uspto-grants-2010_11
Patent number
US07834193B2

Reaction notes

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