Pyridine → Methyl 3-[2-bromo-4-(trifluoromethyl)phenylsulfonamido]thiophene-2-carboxylate

HRID 1925729Notes

Reaction equation

HRID 1925729 reaction equation
[NH2:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]([O:9][CH3:10])=[O:8].N1C=CC=CC=1.[Br:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[S:28](Cl)(=[O:30])=[O:29]>CN(C)C1C=CN=CC=1.ClCCl>[Br:17][C:18]1[CH:23]=[C:22]([C:24]([F:26])([F:25])[F:27])[CH:21]=[CH:20][C:19]=1[S:28]([NH:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]([O:9][CH3:10])=[O:8])(=[O:30])=[O:29]

Participants

6

Reactant 3

HCID 1049PyridineHCID 89652Methyl 3-amino-2-thiophenecarboxylateHCID 27786112-Bromo-4-(trifluoromethyl)benzenesulfonyl chloride

Product 1

HCID 67520727Methyl 3-[2-bromo-4-(trifluoromethyl)phenylsulfonamido]thiophene-2-carboxylateYield 24%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of methyl 3-aminothiophene-2-carboxylate (534.0 mg; 3.4 mmol), 4-dimethylaminopyridine (94.3 mg; 0.77 mmol) and pyridine (2.5 mL; 30.9 mmol) in anhydrous dichloromethane (60 mL) was added 2-bromo-4-(trifluoromethyl)benzene-1-sulfonyl chloride (1.0 g; 3.09 mmol) portion-wise. After addition was complete the reaction mixture was stirred at 0° C. for 20 minutes, gradually allowed to war to room temperature, stirred for 16 hours, and then washed with aqueous hydrochloric acid (50 mL; 2N). The organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by automated silica gel column chromatography (Biotage®) eluting with ethyl acetate/hexanes (0 to 30% v/v over 400 mL gradient elution) to give the title product as a white solid (330 mg).

Workup

  1. additionAfter addition
  2. customgradually allowed to war to room temperature
  3. stirringstirred for 16 hours
  4. washwashed with aqueous hydrochloric acid (50 mL; 2N)
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by automated silica gel column chromatography (Biotage®)
  9. washeluting with ethyl acetate/hexanes (0 to 30% v/v over 400 mL gradient elution)

Sources & evidence

ORD record
ord-becdc2b11b834c789c91aef8b170c43d
Source dataset
uspto-grants-2012_05
Patent number
US08178699B2

Reaction notes

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