2-Thiophenecarboxylic acid → Methyl 3-oxo-3-(thiophen-2-yl)propanoate

In 200 mL of methanol, was dissolved 8.90 g (75.4 mmol) of monomethyl malonate, and the resulting solution was mixed with 4.30 g (37.5 mmol) of magnesium ethoxide, followed by stirring for 4 hours at room temperature. The reaction solution was concentrated and the residue was dried under reduced pressure. In 150 mL of tetrahydrofuran, was dissolved 4.80 g (37.5 mmol) of 2-thiophenecarboxylic acid and the resulting solution was mixed with 6.69 g (41.2 mmol) of carbonyldiimidazole, followed by stirring for 1 hour. The reaction solution was added to a dry magnesium salt and stirred at room temperature for 21 hours. The reaction solution was concentrated; the residue was mixed with 150 mL of 1.5 N hydrochloric acid, extracted with ethyl acetate, and washed with an aqueous sodium hydrogencarbonate solution and then saturated sodium chloride water. The resultant was dried over sodium sulfate anhydride, filtered, and concentrated. The residue was distilled (0.06 mmHg, 87) to give 5.95 g (32.3 mmol, 86.1%) of methyl 2-thiophenecarbonylacetate as an anhydrous liquid. Similarly to Example 133, 2.52 g (8.28 mmol, 81.2%) of yellow crystals were obtained from 5.95 g (32.2 mmol) of methyl 2-thiophenecarbonylacetate by recrystallization from methanol.

1. concentrationThe reaction solution was concentrated
2. customthe residue was dried under reduced pressure
3. stirringby stirring for 1 hour
4. stirringstirred at room temperature for 21 hours
5. concentrationThe reaction solution was concentrated
6. additionthe residue was mixed with 150 mL of 1.5 N hydrochloric acid
7. extractionextracted with ethyl acetate
8. washwashed with an aqueous sodium hydrogencarbonate solution
9. dry with materialThe resultant was dried over sodium sulfate anhydride
10. filtrationfiltered
11. concentrationconcentrated
12. distillationThe residue was distilled (0.06 mmHg, 87)

ORD record

ord-5b09df55843e4375884c95bfb218b9a3

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06215016B1