Acetic Anhydride → HCID 68443950, compound

Temperature

23 °C

2-Formyl-6,7-dihydro-4H-thieno[3,2-c]pyridine-5-carboxylic acid ethyl ester (480 mg, 2 mmol) was dissolved in 20 ml acetonitrile and magnesium bromide etherate (516 mg, 2 mmol) was then added under N2 atmosphere. The mixture was stirred at 23° C. for half an hour. 6-Bromo-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester (770 mg, 2 mmol) in 20 ml THF was then injected all at once and the mixture was immediately cooled to −20° C. Triethylamine (1 ml) was then injected and the mixture stirred at −20° C. for 3 hrs. Then acetic anhydride (0.4 ml) was injected and the mixture was stirred at 0° C. for 48 hrs. The reaction media was then diluted with 200 ml ethyl acetate and washed sequentially with 50 ml 5% citric acid, 50 ml saturated sodium bicarbonate, and 50 ml brine. The organic layer was then dried over sodium sulfate. Filter, concentrate, and flash column chromatograph using 20% ethyl acetate in hexane gave 690 mg (50%, yield) product. A fraction of this product (456 mg, 0.69 mmol) was then dissolved in 15 ml THF and 15 ml aqueous phosphate buffer (pH=6.5). The mixture was then subjected to 40 psi hydrogen for two hrs with 0.5 gram 10% palladium on carbon. Then it was filtered through a pad of celite and concentrated in vacuo to remove most of the THF. The solution was then cooled to zero degree and basified to pH=8 with 1 N sodium hydroxide. Then it was purified via reverse phase HPLC using 2 liter of water followed by 5% acetonitrile in water. Water was then removed through concentrate in vacuo and 18 mg (5%) of product was collected.

1. temperaturewas immediately cooled to −20° C
2. stirringthe mixture stirred at −20° C. for 3 hrs
3. stirringthe mixture was stirred at 0° C. for 48 hrs
4. customThe reaction media
5. washwashed sequentially with 50 ml 5% citric acid, 50 ml saturated sodium bicarbonate, and 50 ml brine
6. dry with materialThe organic layer was then dried over sodium sulfate
7. filtrationFilter
8. concentrationconcentrate
9. customgave
10. custom690 mg (50%, yield) product
11. filtrationThen it was filtered through a pad of celite
12. concentrationconcentrated in vacuo
13. customto remove most of the THF
14. temperatureThe solution was then cooled to zero degree and basified to pH=8 with 1 N sodium hydroxide
15. customThen it was purified via reverse phase
16. customWater was then removed
17. concentrationthrough concentrate in vacuo and 18 mg (5%) of product
18. customwas collected

ORD record

ord-31342fb898a44b98bc2a5b6a99a693f6

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07112582B2