Process for the preparation of 1-(3,5-dichloro-4-fluoro-phenyl)-2,2,2-trifluoro-ethanone
View Patent ↗The invention relates to a process for the preparation of a compound of formula I comprising a) reacting a compound of formula II in the presence of magnesium or an organometallic reagent of formula III R 1 M 2 X (III), wherein R 1 is C I -C 4 alkyl; M 2 is Li or Mg and X is halogen or absent; with a compound of formula IV CF 3 —C(O)—R 2 (IV), wherein R 2 is halogen, hydroxyl, C I -C 4 alkoxy, (di-C I -C 4 alkyl)amino, OC(O)CF 3 , phenoxy or OM 1 ; wherein M 1 is Lithium, Magnesium, Sodium or Potassium; to a compound of formula V, and b) reacting the compound of formula V with alkali metal fluoride in the presence of catalytic amounts of a phase transfer catalyst in the presence of a polar solvent to the compound of formula I.
1. A process for the preparation of the compound of formula I
comprising
a) reacting the compound of formula II
in the presence of magnesium or an organometallic reagent of formula III
R 1 —M 2 X (III),
wherein
R 1 is C 1 -C 4 alkyl;
M 2 is Lithium or Magnesium and
X is halogen or absent;
with a compound of formula IV
CF 3 —C(O)—R 2 (IV),
wherein R 2 is halogen, hydroxyl, C 1 -C 4 alkoxy, (di-C 1 -C 4 alkyl)amino, OC(O)CF 3 , phenoxy or OM 1 ; wherein
M 1 is Lithium, Magnesium, Sodium or Potassium;
to the compound of formula V,
and
b) reacting the compound of formula V with an alkali metal fluoride in the presence of catalytic amounts of a phase transfer catalyst in the presence of a polar solvent to the compound of formula I.
2. A process according to claim 1 , comprising
a) reacting the compound of formula II
in the presence of an organometallic reagent of formula III
R 1 —M 2 X (III)
wherein
R 1 is C 1 -C 4 alkyl;
M 2 is Lithium or Magnesium and
X is halogen or absent.
3. A process according to claim 2 , wherein the organometallic reagent is isopropylmagnesiumchloride complexed with LiCl.
4. A process according to claim 1 , wherein the alkali metal fluoride is selected from KF, LiF and NaF.
5. A process according to claim 1 , wherein the phase transfer catalyst is selected from the group consisting of phosphonium salts of general formula (R 3 ) 4 PX and ammonium salts of general formula (R 3 ) 4 NX wherein R 3 is C 1 -C 4 alkyl or phenyl and X is halogen.
6. A process according to claim 1 , wherein the polar solvent is selected from the group consisting of sulfolane, dimethylformamide and dimethylsulfoxide.
7. A process according to claim 1 , comprising
a) reacting the compound of formula II
in the presence of an organometallic reagent of formula III
R 1 —M 2 X (III)
wherein
R 1 is C 1 -C 4 alkyl;
M 2 is Lithium or Magnesium and
X is halogen or absent;
with a compound of formula IV
CF 3 —C(O)—R 2 (IV),
wherein R 2 is halogen, hydroxyl, C 1 -C 4 alkoxy, (di-C 1 -C 4 alkyl)amino, OC(O)CF 3 , phenoxy or OM 1 ; wherein
M 1 is Lithium, Magnesium, Sodium or Potassium;
to the compound of formula V,
and
b) reacting the compound of formula V with an alkali metal fluoride selected from KF, LiF and NaF in the presence of catalytic amounts of a phase transfer catalyst selected from the group consisting of phosphonium salts of general formula (R 3 ) 4 PX and ammonium salts of general formula (R 3 ) 4 NX wherein R 3 is C 1 -C 4 alkyl or phenyl and X is halogen; in the presence of a polar solvent selected from the group consisting of sulfolane, dimethylformamide and dimethylsulfoxide, to the compound of formula I.
8. A process according to claim 7 , wherein the organometallic reagent is isopropylmagnesiumchloride complexed with LiCl.