N-[4-Cyano-3-(trifluoromethyl)phenyl]-2-methyloxirane-2-carboxamide → Bicalutamide

HRID 2415423Notes

Reaction equation

HRID 2415423 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2([CH3:15])[CH2:14][O:13]2)=[O:11])=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2].[F:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([O-:29])=[O:28])=[CH:23][CH:22]=1.[Na+]>C(Cl)(Cl)Cl.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:15][C:12]([OH:13])([C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:5]=1)=[O:11])[CH2:14][S:27]([C:24]1[CH:23]=[CH:22][C:21]([F:20])=[CH:26][CH:25]=1)(=[O:29])=[O:28]

Participants

6

Reactant 2

HCID 10149314N-[4-Cyano-3-(trifluoromethyl)phenyl]-2-methyloxirane-2-carboxamideHCID 236662204-fluorobenzenesulfinic acid sodium salt

Product 1

HCID 2375Bicalutamide

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6212ChloroformSolvent2×

Procedure

0.500 g of the epoxyamide (5A) was dissolved in a mixture of 40 ml of chloroform and 40 ml of water and 371 mg of sodium p-fluorobenzenesulfinate was added. Subsequently, 298 mg of tetrabutylammonium bromide was added. The reaction mixture was heated till reflux, while stirring vigorously. The reaction was monitored with HPLC. After 96 hours of reflux, the reaction mixture was cooled to room temperature. 20 ml of chloroform was added and the organic layer was washed with 3×50 ml of water, dried (Na2SO4) and evaporated to dryness. Yield: 860 mg. Purification of the crude product by column chromatography (Merck silica gel 60; eluent: heptane/ethyl acetate=1/1) afforded bicalutamide as white solid. Isolated yield: 380 mg (48%). 1H-NMR: confirmed the structure.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was heated
  3. temperaturetill reflux
  4. temperatureAfter 96 hours of reflux
  5. washthe organic layer was washed with 3×50 ml of water
  6. dry with materialdried (Na2SO4)
  7. customevaporated to dryness
  8. customPurification of the crude product by column chromatography (Merck silica gel 60; eluent: heptane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-708456326e6f44d09c579078ccc42191
Source dataset
uspto-grants-2004_11
Patent number
US06818766B2

Reaction notes

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