Carbon Dioxide → HCID 66617149, compound

Temperature

-78 °C

In a 50-mL round bottom flask under nitrogen was dissolved 4,4-diethoxybut-1-yne (10.14 g, 71.3 mmol) in THF (102 mL), and stirred at −78° C. Butyllithium (30.0 mL, 74.9 mmol) was added dropwise, and after 15 minutes, carbon dioxide (157 g, 3566 mmol) was bubbled through the reaction mixture, as it was warmed to RT for 1 h. The reaction was degassed with argon for 20 minutes to eliminate excess CO2, and was then cooled to 0° C., and neutralized with 3-methylisothiazol-5-amine hydrochloride (12.21 g, 107 mmol). To the reaction mixture was added HATU (35.2 g, 93 mmol) followed by Hunig's Base (37.4 mL, 214 mmol). The reaction was slowly allowed to warm to RT and stirred for 2 h. The reaction mixture was diluted with 1N NaOH (500 mL), and then extracted with small amounts of EtOAc (3×150 mL). The combined organics were extracted with 1N NaOH (500 mL) and the organics were discarded. The basic aqueous layers were combined, neutralized with 2N HCl, and extracted with ether. The organics were dried with sodium sulfate, filtered and concentrated in vacuo to yield crude material contaminated with tetramethylurea, and acetic acid. The acetic acid was removed via dilution with ethyl acetate and subsequent washing with sat. aq. sodium bicarbonate. After washing with sodium bicarbonate, the resulting product was dried with magnesium sulfate, filtered and concentrated in vacuo to yield 5,5-diethoxy-N-(3-methylisothiazol-5-yl)pent-2-ynamide as a dark-red oil.

1. temperaturewas warmed to RT for 1 h
2. customThe reaction was degassed with argon for 20 minutes
3. temperaturewas then cooled to 0° C.
4. temperatureto warm to RT
5. stirringstirred for 2 h
6. extractionextracted with small amounts of EtOAc (3×150 mL)
7. extractionThe combined organics were extracted with 1N NaOH (500 mL)
8. extractionextracted with ether
9. dry with materialThe organics were dried with sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto yield crude material
13. customThe acetic acid was removed via dilution with ethyl acetate
14. washsubsequent washing with sat. aq. sodium bicarbonate
15. washAfter washing with sodium bicarbonate
16. dry with materialthe resulting product was dried with magnesium sulfate
17. filtrationfiltered
18. concentrationconcentrated in vacuo

ORD record

ord-b08e925a69f44840918835e08ec4e307

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691838B2