Acetamide → Ethyl 2-fluorooctanoate

Temperature

80 °C

--A mixture of acetamide (49 g) and ethyl 2-bromooctanoate 64 (100 ml, 0.464 mol) was heated at 80° C. (reaction temperature) with mechanical stirring under nitrogen until homogeneous. Anhydrous potassium fluoride (49.3 g, 0.84 mol) was added followed by tetrabutylammonium fluoride (3.25 ml). The mixture was heated for 5 h at 140° C. with rapid stirring and allowed to cool to 90° C. prior to pouring into ice (400 ml). The reaction vessel was rinsed with water and dichloromethane which were added to the ice mixture. The aqueous phase was extracted with dichloromethane (3 times); the combined organic solutions were dried (Na2SO4) and filtered. The solution was cooled to 5° C. under nitrogen and bromine (19.3 ml, 0.375 mol) was added. After 3 h saturated sodium thiosulfate solution (150 ml) was added. The organic phase was washed with sat. sodium bicarbonate solution (twice) and brine, dried (Na2SO4) and evaporated. The residue was distilled to give pure ethyl 2-fluorooctanoate 65 (33.9 g, 38%); b.p. 56-61° C. at 0.5 mm Hg; νmax /cm-1 (film) 2930, 2860, 1760, 1740, 1370, 1275, 1205, 1090 and 1030; δ 0.88 (3H, t, Me), 1.20-1.56 (11H, m), 1.75-2.13 (2H, m), 4.26 (2H, q, ) and 4.90(1H, 2JHF 46 and J8, CHF); m/z 190 (M+), 185, 168, 161, 143, 129, 113 and 106.

1. custom(reaction temperature)
2. temperatureThe mixture was heated for 5 h at 140° C.
3. stirringwith rapid stirring
4. temperatureto cool to 90° C.
5. washThe reaction vessel was rinsed with water and dichloromethane which
6. additionwere added to the ice mixture
7. extractionThe aqueous phase was extracted with dichloromethane (3 times)
8. dry with materialthe combined organic solutions were dried (Na2SO4)
9. filtrationfiltered
10. temperatureThe solution was cooled to 5° C. under nitrogen
11. washThe organic phase was washed with sat. sodium bicarbonate solution (twice) and brine
12. dry with materialdried (Na2SO4)
13. customevaporated
14. distillationThe residue was distilled

ORD record

ord-bcb46bbce11a49378e66d294ea049758

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05986096