Aniline → N-(3-Iodo-4-methylphenyl)thiophene-3-carboxamide
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
Reactant 5
Product 1
Reagents, catalysts & solvents 3
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-fa45ae3cfc5d4a0f9ae4043556b1968c
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08207176B2
Reaction notes
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