Acetonitrile → 2-Thenoylacetonitrile

Temperature

-50 °C

To a flask charged with THF (250 ml) was added dropwise n-butyl lithium (18.4 mL, 46 mmol) at −78° C. under a N2 atmosphere. After addition the resulting solution warmed to −50° C. and dry MeCN (1.86 g, 45 mmol) was added slowly. After 1 h, the reaction was cooled to −78° C. and was treated with thiophene-2-carboxylic acid ethyl ester (6.93 g, 44.5 mmol). After stirring for 1 h the resulting mixture was warmed to RT and stirred for 1 h. Water was added dropwise at 0° C. to quench the reaction and the solution was extracted with ethyl acetate (3×200 mL). The organic layers were combined, washed with brine, dried (Na2SO4) and the solvent was evaporated under reduced pressure to give a solid residue, which was re-crystallized from CH2Cl2. After the solid was collected by filtration, they were redissolved in ethyl acetate (100 mL), and acidified with dilute hydrochloride (2N). The aqueous layer was extracted with ethyl acetate (3×200 mL) and the combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated to yield 3-oxo-3-thiophen-2-yl-propionitrile (4.7 g, yield=70%) as a yellow solid, which was used directly in the next step without purification.

1. additionAfter addition the resulting solution
2. temperaturethe reaction was cooled to −78° C.
3. temperaturewas warmed to RT
4. stirringstirred for 1 h
5. customto quench
6. customthe reaction
7. extractionthe solution was extracted with ethyl acetate (3×200 mL)
8. washwashed with brine
9. dry with materialdried (Na2SO4)
10. customthe solvent was evaporated under reduced pressure
11. customto give a solid residue, which
12. customwas re-crystallized from CH2Cl2
13. filtrationAfter the solid was collected by filtration, they
14. dissolutionwere redissolved in ethyl acetate (100 mL)
15. extractionThe aqueous layer was extracted with ethyl acetate (3×200 mL)
16. washthe combined organic layers were washed with brine
17. dry with materialdried (Na2SO4)
18. filtrationfiltered
19. concentrationconcentrated

ORD record

ord-8b8112e754504c04b24ecbc163b86101

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163756B2