N-Methoxy-N-methylacetamide → 5-Acetyl-2-fluorobenzaldehyde

Temperatur

-40 °C

2-(5-bromo-2-fluorophenyl)-1,3-dioxolane (5.2 g, 21.2 mmol) is taken up in dry, preservative-free THF (30 mL) and the solution is cooled to −40° C. under N2. A 1.6 M solution of n-butyllithium in hexanes (13.2 mL, 1 eq) is added via syringe and the solution is stirred for 25 minutes @−40° C. The lithiated substrate is added dropwise via cannula to a −40° C. solution of N-methoxy-N-methylacetamide (2.36 mL, 22.2 mmol, Aldrich) in 10 mL of dry, preservative-free THF. The solution is warmed to RT with stirring for 1 hour. The solution is poured into a flask containing 1.0M HCl (100 mL) and heated to 65° C. with vigorous stirring overnight. Upon cooling the oily product is extracted into EtOAc (200 mL) and the organic layer is washed with water and brine (200 mL each). The organic layer is dried over Na2SO4 and filtered. The solvent is removed by rotary evaporation and the product is purified on a Biotage Flash 75L (800 g silica) cartridge using 30% MTBE in heptane as eluent. The product containing fractions are pooled and the solvent is removed by rotary evaporation. The product is dried under vacuum yielding an oily yellow solid.

1. customin dry
2. customof dry
3. temperatureThe solution is warmed to RT
4. stirringwith stirring for 1 hour
5. additionThe solution is poured into a flask
6. additioncontaining 1.0M HCl (100 mL)
7. temperatureheated to 65° C.
8. stirringwith vigorous stirring overnight
9. temperatureUpon cooling the oily product
10. extractionis extracted into EtOAc (200 mL)
11. washthe organic layer is washed with water and brine (200 mL each)
12. dry with materialThe organic layer is dried over Na2SO4
13. filtrationfiltered
14. customThe solvent is removed by rotary evaporation
15. customthe product is purified on a Biotage Flash 75L (800 g silica) cartridge
16. additionThe product containing fractions
17. customthe solvent is removed by rotary evaporation
18. customThe product is dried under vacuum
19. customyielding an oily yellow solid

ORD-Eintrag

ord-ce856177fc50424f8b75cc4d7da03a4d

Quelldatensatz

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08420646B2