Aniline → N-(3-Iodo-4-methylphenyl)thiophene-3-carboxamide

HRID 2245054Notes

Reaction equation

[S:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=O)=[CH:2]1.C(Cl)(=O)C(Cl)=O.[CH3:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=1[I:23])N.C([O-])([O-])=O.[K+].[K+].[NH2:30]C1C=CC=CC=1>C(Cl)Cl.CN(C=O)C.N1C=CC=CC=1>[I:23][C:22]1[CH:21]=[C:20]([NH:30][C:6]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)=[O:8])[CH:18]=[CH:17][C:16]=1[CH3:15]

Participants

Conditions

Temperature: 0 °C

Procedure

3-Thiophenecarboxylic acid (2.0 g, 15.6 mmol) was dissolved in methylene chloride (100 mL) and 2 drops of DMF were added. The mixture was cooled to about 0° C. and oxalyl chloride (1.5 mL, 17.1 mmol) was added slowly and allowed to warm to room temperature. Gas evolution was observed during warming. 3-Methyl-4-iodoaniline (5.45 g, 23.5 mmol), 4 drops of pyridine and K2CO3 (2.58 g, 18.7 mmol) are dissolved in CH2Cl2 (10 mL) and cooled to about 0° C. After about 1 h, the acid chloride mixture is slowly added to the cooled aniline mixture and allowed to warm to room temperature and stirred for about 18 h. The resulting mixture is filtered, washed with ethyl acetate and the filtrate is concentrated to a brown oil. The crude material was purified via flash chromatography (10-30% ethyl acetate in hexanes) to afford the desired product (1.56 g, 29%) as an off-white solid.

Workup

temperatureto warm to room temperature
temperatureduring warming
temperaturecooled to about 0° C
temperatureto warm to room temperature
filtrationThe resulting mixture is filtered
washwashed with ethyl acetate
concentrationthe filtrate is concentrated to a brown oil
customThe crude material was purified via flash chromatography (10-30% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-d85927569a29493294b785c28614e110
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07678801B2

Reaction notes

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