4-(Methylsulfonyl)aniline → HCID 178491240, compound

HRID 1166334Notes

Reaction equation

HRID 1166334 reaction equation
[CH3:1][S:2]([C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C[Al](C)C.[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[C:20]#[N:21]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[F:16][C:17]1[CH:18]=[C:19]([C:20](=[NH:21])[NH:9][C:8]2[CH:10]=[CH:11][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:6][CH:7]=2)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]

Participants

6

Reactant 3

HCID 796174-(Methylsulfonyl)anilineHCID 27745483-Fluoro-4-methoxybenzonitrileHCID 16682925Trimethylaluminum

Product 1

HCID 178491240HCID 178491240, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6212ChloroformSolvent

Procedure

To a suspension of 4-(methylsulfonyl)aniline (2.82 g, 16.5 mmol) in toluene (150 mL), trimethylaluminum (2M solution in toluene, 12.5 mL, 24.7 mmol) was added over 15 minutes. The reaction mixture was warmed to room temperature and stirred for 2.5 hours. A solution of 3-fluoro-4-methoxybenzonitrile (5 g, 33 mmol) in toluene (100 mL) was added over 10 minutes and the reaction mixture was heated to 80-85° C. After 20 hours, the reaction mixture was cooled to room temperature and poured over a slurry of silica gel in chloroform. After filtration, the residue was washed with a mixture of methylene chloride/methanol (2/1). The combined filtrates were concentrated in vacuo and the resulting yellowish solid was stirred with a mixture of hexane/ether (2/1, 1000 mL). The intermediate was filtered and washed with more hexane/ether (2/1). The pale yellow solid 3-fluoro-4-methoxy-N-(4-(methylsulfonyl)phenyl]benzenecarboximidamide (3.95 g, 74%) was used in the next reaction without further purification: mp (DSC) 195C. Anal. Calc'd. for C15H15N2SO3F: C, 55.89, H, 4.69, N, 8.69. Found: C, 55.92, H, 4.74, N, 8.53.

Workup

  1. additionwas added over 15 minutes
  2. temperaturethe reaction mixture was heated to 80-85° C
  3. waitAfter 20 hours
  4. temperaturethe reaction mixture was cooled to room temperature
  5. filtrationAfter filtration
  6. washthe residue was washed with a mixture of methylene chloride/methanol (2/1)
  7. concentrationThe combined filtrates were concentrated in vacuo
  8. stirringthe resulting yellowish solid was stirred with a mixture of hexane/ether (2/1, 1000 mL)
  9. filtrationThe intermediate was filtered
  10. washwashed with more hexane/ether (2/1)
  11. customThe pale yellow solid 3-fluoro-4-methoxy-N-(4-(methylsulfonyl)phenyl]benzenecarboximidamide (3.95 g, 74%) was used in the next reaction without further purification

Sources & evidence

ORD record
ord-94e1651d96374ff69e3c1e4799125a38
Source dataset
uspto-grants-2003_09
Patent number
US06613789B2

Reaction notes

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