Acetonitrile → 2,6-Difluoro-3-methoxybenzonitrile

Temperatur

0 °C

To an ice cold solution of DMF (0.45 ml) and acetonitrile (10 ml) was added oxalyl chloride (0.41 g, 0.28 ml, 3.20 mmol) dropwise while maintaining the temperature to 0° C. The reaction mixture was stirred at 0° C. for 40 min followed by addition of a solution of 2,6-difluoro-3-methoxybenzamide (0.50 g, 2.70 mmol) in DMF (4.5 ml).The resulting reaction mixture was stirred at 0° C. 40 min and then allowed to come to room temperature. After completion of reaction (10 min, TLC monitoring), triethyl amine (0.57 g, 0.80 ml, 5.67 mmol) was added dropwise. The reaction mass was concentrated in vacuo followed by addition of water (100 ml) and extraction with ethyl acetate (3×100 ml). The combined organics was washed with water, brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified over silica gel (60-120 M, 10% EtOAc-Hexane) to get the desired product (0.30 g, 66%) as a white solid.

1. customresulting
2. customreaction mixture
3. stirringwas stirred at 0° C
4. custom40 min
5. customto come to room temperature
6. additionwas added dropwise
7. concentrationThe reaction mass was concentrated in vacuo
8. additionfollowed by addition of water (100 ml) and extraction with ethyl acetate (3×100 ml)
9. washThe combined organics was washed with water, brine
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude residue was purified over silica gel (60-120 M, 10% EtOAc-Hexane)

ORD-Eintrag

ord-684e7acc92c545c3ab8af53c5a4710b2

Quelldatensatz

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08415383B2