3-Chloro-2-methylaniline → 2-(3-Chloro-2-methylphenyl)thiophene
Reaction equation
[Cl:1][C:2]1[C:3]([CH3:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)N.C(ON=O)(C)(C)C.[S:17]1[CH:21]=[CH:20][CH:19]=[CH:18]1>>[Cl:1][C:2]1[C:3]([CH3:9])=[C:4]([C:18]2[S:17][CH:21]=[CH:20][CH:19]=2)[CH:6]=[CH:7][CH:8]=1Participants
Procedure
3-Chloro-2-methylaniline was treated with t-butylnitrite in excess thiophene as described in J. Chem. Soc., 4257 (1963) to produce 2-(3-chloro-2-methylphenyl)thiophene as an oil. Reaction of the oil with N-bromosuccinimide as described in J. Am. Chem. Soc., 89, 2348 (1967) yielded 2-(2-bromomethyl-3-chlorophenyl)thiophene as an oil, which was reacted without further purification, as described in J. Chem. Soc., 2708 (1955), with diethyl malonate in the presence of tetrabutyl ammonium bromide and potassium hydroxide in dry tetrahydrofuran, producing ethyl [2-carboethoxy-3-[2-chloro-6-(thien-2-yl)phenyl]]propionate. Hydrolysis of the latter with hydrochloric acid in glacial acetic acid provided 3-[2-chloro-6-(thien-2-yl)phenyl]propionic acid; mp 83°-86°.
Sources & evidence
- ORD record
- ord-6dd2cef81a444b8a86f8eb351140693e
- Source dataset
- uspto-grants-1984_12
- Patent number
- US04487778
Reaction notes
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