Diisopropylamine → 5-(Ethoxycarbonyl)thiophene-2-carboxylic acid

Temperature

0 °C

To a solution of diisopropylamine (3.6 mL, 25.75 mmol) in 10 mL of THF at -78° C. under argon was added a 1.6M solution of n-butyllithium in hexane (16.1 mL, 25.75 mmol). The mixture was stirred for 15 min, and a solution of 2-thiophenecarboxylic acid 34 (1.5 g, 11.705 mmol) (2-thiophenecarboxylic acid 34 is readily available from Aldrich) in 5 mL of THF was added slowly. The mixture was stirred for 15 min, and ethyl chloroformate (2.7 mL, 28.33 mmol) was added. The mixture was stirred for 30 min at -78° C., and warmed to 0° C. for another 30 min. The reaction mixture was poured into saturated aqueous NaHCO3, and washed with 80% ethyl acetate/hexane. The aqueous layer was acidified with acetic acid and extracted with 80% ethyl acetate/hexane. The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated to afford a yellow solid. Flash chromatography yielded the desired acid 35 (1.76 g, 75%) as a white solid: m.p. >300° C. The structure of the product was also confirmed using IR, 1H NMR and mass spectroscopy.

1. additionwas added slowly
2. stirringThe mixture was stirred for 15 min
3. stirringThe mixture was stirred for 30 min at -78° C.
4. washwashed with 80% ethyl acetate/hexane
5. extractionextracted with 80% ethyl acetate/hexane
6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a yellow solid

ORD record

ord-ebbfc8b320114155b8162abef78f6799

Source dataset

uspto-grants-1995_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05466861