2-Fluoroaniline → (5-bromo(2-thienyl))-N-(2-fluorophenyl)carboxamide

HRID 1524223Notes

Reaction equation

HRID 1524223 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[F:16][C:17]1[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=1[NH2:19].CCN(C(C)C)C(C)C>C(Cl)Cl.[Cl-].[Na+].O.CC(=O)OCC.CN(C=O)C>[Br:1][C:2]1[S:6][C:5]([C:7]([NH:19][C:18]2[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=2[F:16])=[O:9])=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 95842-FluoroanilineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 3491155-Bromothiophene-2-carboxylic acid

Product 1

HCID 26584369(5-bromo(2-thienyl))-N-(2-fluorophenyl)carboxamideYield 89%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 5-bromo-thiophene-2-carboxylic acid (5) (207 mg, 1 mmol), oxalyl chloride (420 μl) and catalytic amount of DMF in 5 ml DCM was stirred at r.t for 2 h before evaporation to dryness. The resulting solid residue was dissolved in 5 ml DCM and to which were added 2-fluoroaniline (193 μl, 2 eq) and DIEA (522 μl). The reaction mixture was stirred at r.t for overnight before worked up with EA/aq. HO/brine. The org. phase was concentrated and then purified on a flash silica gel column to give 267 mg (5-bromo(2-thienyl))-N-(2-fluorophenyl)carboxamide (9) as off-white solid. (yield: 89%, purity>95%).

Workup

  1. stirringThe reaction mixture was stirred at r.t for overnight
  2. concentrationphase was concentrated
  3. custompurified on a flash silica gel column

Sources & evidence

ORD record
ord-93149421a18b4485ae160faf4420b115
Source dataset
uspto-grants-2015_07
Patent number
US09079891B2

Reaction notes

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