Water → 2-(2-Nitro-4-trifluoromethyl-phenylamino)-benzo[b]thiophene-3-carbonitrile

HRID 131368

Reaction equation

HRID 131368 reaction equation
[NH2:1][C:2]1[S:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[C:3]=1[C:11]#[N:12].F[C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:15]=1[N+:24]([O-:26])=[O:25].[OH-].[Li+].O>CS(C)=O.ClCCl>[N+:24]([C:15]1[CH:16]=[C:17]([C:20]([F:21])([F:22])[F:23])[CH:18]=[CH:19][C:14]=1[NH:1][C:2]1[S:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[C:3]=1[C:11]#[N:12])([O-:26])=[O:25]

Participants

7

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 677784-Fluoro-3-nitrobenzotrifluorideHCID 232735812-Amino-1-benzothiophene-3-carbonitrile

Product 1

HCID 586260492-(2-Nitro-4-trifluoromethyl-phenylamino)-benzo[b]thiophene-3-carbonitrileYield 63.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

Combine 2-amino-benzo[b]thiophene-3-carbonitrile (3.48 g, 20.0 mmol), 1-Fluoro-2-nitro-4-trifluoromethyl-benzene (4.31 g, 20.0 mmol), and lithium hydroxide (0.958 g, 40.0 mmol) in anhydrous dimethylsulfoxide (50 mL), and heat at 55° C. for 2 hours. Cool to ambient temperature, pour into a beaker filled with ice/deionized water (50 mL), and stir for 30 minutes. Add deionized water and dichloromethane and then separate the organic layer. Extract the aqueous layer with dichloromethane many times. Then wash the organics with deionized water (3×). Combine the washes and back extract them with dichloromethane. Wash the organics with a saturated solution of sodium chloride, and back extract the combined washes with dichloromethane. Dry (sodium sulfate), filter, and concentrate the organics under reduced pressure to a residue. After triturating the residue with methanol, isolate the resulting solid by suction filtration, wash with methanol, and dry at ambient temperature under reduced pressure to give the title compound (4.61 g). Concentrate the filtrate under reduced pressure and purify by flash chromatography, eluting with a gradient of ethyl acetate: dichloromethane: hexane (0.25:5:5, 0-100% in hexane) to give the title compound (0.53 g). Total solid: 5.14 g (70.8%). NMR (1H, 300 MHz, CDCl3), δ (ppm): 10.26 (s, 1H), 8.63-8.56 (m, 1H), 7.93-7.85 (m, 1H), 7.84-7.75 (m, 2H), 7.64-7.45 (m, 3H).

Workup

  1. additionpour into a beaker
  2. customseparate the organic layer
  3. extractionExtract the aqueous layer with dichloromethane many times
  4. washThen wash the organics with deionized water (3×)
  5. extractionCombine the washes and back extract them with dichloromethane
  6. washWash the organics with a saturated solution of sodium chloride
  7. extractionback extract the combined washes with dichloromethane
  8. dry with materialDry (sodium sulfate)
  9. filtrationfilter
  10. concentrationconcentrate the organics under reduced pressure to a residue
  11. customAfter triturating the residue with methanol
  12. customisolate the resulting solid
  13. filtrationby suction filtration
  14. washwash with methanol
  15. customdry at ambient temperature under reduced pressure

Sources & evidence

ORD record
ord-78e752b0bec446ccbbf7a9fa085f7d9d
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Linked notes

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