4-Methoxy-2-thiophenecarboxylic acid ethyl ester → 4-Methoxythiophene-2-carboxylic acid

3-Methoxythiophene (4.0 ml) was dissolved in tetrahydrofuran (50 ml), and the mixture was cooled to -78° C. n-Butyllithium (1.6M in hexane, 19.5 ml) was slowly added dropwise, and the mixture was stirred at the same temperature for 1 hour. The mixture was poured into a mixture of dry ice and diethyl ether, and warmed to room temperature with stirring. The solvent was distilled off, and the residue was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a mixture of 3-methoxy-2-thiophenecarboxylic acid and 4-methoxy-2-thiophenecarboxylic acid (6.0 g). This mixture was dissolved in N,N-dimethylformamide (50 ml), and iodothane (3.0 ml) and potassium carbonate (5.25 g) were added. The mixture was stirred at room temperature for 15 hours, poured into water and extracted with diethyl ether. The extract was washed with 5% aqueous potassium hydrogen sulfate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the desired fractions were concentrated under reduced pressure to give 4-methoxy-2-thiophenecarboxylic acid ethyl ester (2.69 g) and 3-methoxy-2-thiophenecarboxylic acid ethyl ester (3.98 g). 4-Methoxy-2-thiophenecarboxylic acid ethyl ester (2.69 g) was dissolved in a mixture of ethanol (25 ml) and tetrahydrofuran (25 ml), and 1N aqueous sodium hydroxide (22 ml) was added. The mixture was stirred at room temperature for 3 hours and washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 4-methoxy-2-thiophenecarboxylaic acid (2.11 g) as crystals.

1. additionwas added
2. washwashed with diethyl ether
3. extractionextracted with ethyl acetate
4. dry with materialThe extract was dried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customto give 4-methoxy-2-thiophenecarboxylaic acid (2.11 g) as crystals

ORD record

ord-19a0af1b32a04e82b50535ac82eeebf1

Source dataset

uspto-grants-1998_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05840917