Pyridine → Methyl 4-bromo-5-cyanothiophene-2-carboxylate

To a solution of 16.48 g (66.17 mmol) of methyl 4-bromo-5-formylthiophene-2-carboxylate in 165 mL of acetonitrile was added 5.06 g (72.78 mmol) of hydroxylamine hydrochloride. To this suspension 32.05 mL (397 mmol) of pyridine was added dropwise over a period of 20 min at 20-25° C. After 90 min stirring, neat trifluoroacetic anhydride (22.5 mL, 158.8 mmol) was dropped in over 30 min at room temperature. After 2.5 hours stirring, the reaction mass was poured in a mixture of HCl 0.5 M (200 mL) and ethyl acetate (150 mL); the aqueous layer was extracted again with 150 mL of ethyl acetate. The combined organic extracts were concentrated under reduced pressure and washed again with 120 mL of HCl 1 M. The organic was concentrated under vacuum to afford a raw solid product. This crude material was taken up in 75 mL of ethanol and treated with 75 mL of water under efficient stirring. The resulting suspension was cooled to 0/+4° C., then filtered off to afford 15.4 g of product as light cream solid.

1. stirringAfter 2.5 hours stirring
2. extractionthe aqueous layer was extracted again with 150 mL of ethyl acetate
3. concentrationThe combined organic extracts were concentrated under reduced pressure
4. washwashed again with 120 mL of HCl 1 M
5. concentrationThe organic was concentrated under vacuum
6. customto afford a raw solid product
7. temperatureThe resulting suspension was cooled to 0/+4° C.
8. filtrationfiltered off

ORDレコード

ord-560e1ea9d42a4f68a48b2e3eecfbbe57

出典データセット

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07485661B2