Sodium hydride → (3-Azidopropyl)oxyacetic Acid

A solution of 3-azidopropanol (70.1 g, 0.693 mol) in 100 mL of THF was added dropwise, in a period of 1.5 hours, to a mechanically stirred suspension of NaH (60% in mineral oil, 30.5 g, 0.763 mol) in 250 mL of THF. During the addition of 3-azidopropanol, a gentle reflux was maintained. This was followed by addition of solid Nal (10.4 g, 69.3 mmol), and tetrabutylammonium bromide (22.3 g, 69.3 mmol), and sodium chloroacetate (88.8 g, 0.763 mol). The reaction mixture was heated at reflux temperature for 19 hours, cooled, quenched initially with 20 mL of water (added dropwise) and then with 700 mL of water, washed with EtOAc (3×200 mL), acidified with concentrated HCl to pH=2, and extracted with dichloromethane (6×100 mL). The combined dichloromethane extracts were dried (MgSO4), and the solvent was removed in vacuo to give 63.3 g (58%) of the title compound as a yellow viscous oil. The crude product was used in the next step after spectral characterization.

1. temperaturea gentle reflux
2. temperaturewas maintained
3. temperatureThe reaction mixture was heated
4. temperatureat reflux temperature for 19 hours
5. temperaturecooled
6. customquenched initially with 20 mL of water (
7. additionadded dropwise) and then with 700 mL of water
8. washwashed with EtOAc (3×200 mL)
9. extractionextracted with dichloromethane (6×100 mL)
10. dry with materialThe combined dichloromethane extracts were dried (MgSO4)
11. customthe solvent was removed in vacuo

ORD record

ord-3d8256d7f9844c0dbcea6cc44f2a82af

Source dataset

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05767131