Hydrochloric Acid → Ethyl 4-(2-azidoethoxy)-3-oxobutanoate

Temperature

-30 °C

To a slurry of sodium hydride (0.80 g, 60% dispersion, 20 mmol) in anhydrous THF (10 mL) cooled to −30° C. with a dry ice-acetone bath under N2 was slowly added a solution of 4-chloroacetoacetate (3.25 g, 19.75 mmol) in anhydrous THF (10 mL). The mixture was kept cooled at −30° C. and stirred for 30 min. This solution was transferred by cannula to another flask containing a slurry of sodium hydride (0.80 g, 60% dispersion, 20 mmol) and 2-azido-ethanol (1.72 g, 19.8 mmol) in anhydrous THF (30 mL). After the addition, the temperature was allowed to warm up to RT and stirred overnight (ca. 15 h). The mixture was acidified with 1N HCl and then extracted with EtOAc (100 mL). The EtOAc extract was washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo to afford 4.792 g of crude product as a brown oil. The crude product was purified by chromatography using the ISCO Combiflash SQ16× (120 g Redisep silica gel column, 0 to 70% EtOAc in hexanes for 30 min at 40 mL/min) to afford 2.932 g of purified material as a yellow oil.

1. customThis solution was transferred by cannula to another flask
2. additionAfter the addition
3. temperatureto warm up to RT
4. stirringstirred overnight (ca. 15 h)
5. extractionextracted with EtOAc (100 mL)
6. extractionThe EtOAc extract
7. washwas washed with brine (50 mL)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto afford 4.792 g of crude product as a brown oil
12. customThe crude product was purified by chromatography

ORD record

ord-e5e9a01377af47a88958602307957285

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07166603B2