Hydrochloric Acid → 4-Acetyl-2,2-difluoro-1,3-benzodioxole

Temperatur

-10 °C

6.2 g (55 mmol) of potassium tert.-butoxide dissolved in 40 ml of tetrahydrofuran (THF) are added dropwise at -30° C. under argon, over a period of 20 minutes, to a solution of 8.0 g (50 mmol) of 2,2-difluoro-1,3-benzodioxole in 10 ml of THF in a 250 ml 3-necked flask. The mixture is then cooled to -90° C. (methanol/liquid nitrogen), and 35 ml (55 mmol) of n-butyllithium (1.58 M in hexane) are added thereto over a period of 30 minutes. The deep red solution of 2,2-difluoro-1,3-benzodioxol-4-yl-potassium is maintained at -78° C. for 20 minutes. Then, 5.2 g (50 mmol) of N-methyl-N-methoxy-acetamide in 20 ml of THF are added thereto over a period of 15 minutes at -78° C. When the dropwise addition is complete, the beige reaction mixture is allowed to warm up to -10° C. and is then hydrolysed with 40 ml of 10% hydrochloric acid. The hydrolysed mixture is extracted three times with 70 ml of diethyl ether each time. The organic solutions are washed three times with 30 ml of 1N HCl each time, dried over Na2SO4 and concentrated in a vacuum rotary evaporator. Upon distillation of the residue, 7.1 g (79%) of the product distil over in the form of a colourless oil at boiling point (b.p.) 114°-116° C./30 mbar. 1H-NMR (CDCl3 ; 300 MHz): 7.65 (d×d; J 7.9; 1.5; 1H); 7.27 (d×d; J 7.9; 1.5; 1H); 7.18 (t; J 7.9; 1H); 2.68 (s; 3H).

1. additionare added
2. waitover a period of 15 minutes at -78° C
3. additionWhen the dropwise addition
4. extractionThe hydrolysed mixture is extracted three times with 70 ml of diethyl ether each time
5. washThe organic solutions are washed three times with 30 ml of 1N HCl each time
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in a vacuum rotary evaporator
8. distillationUpon distillation of the residue, 7.1 g (79%) of the product
9. customdistil over in the form of a colourless oil at boiling point (b.p.) 114°-116° C./30 mbar

ORD-Eintrag

ord-318e046592b5463db6690a40358dcb47

Quelldatensatz

uspto-grants-1996_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05493032