Reacción #52049

Ecuación de reacción

methyl 3-cyclopropyl-3-oxopropionate

2-amino-4′-fluorobenzophenone methanesulfonate

→

methyl 2-cyclopropyl-4-(4′-fluorophenyl)quinoline-3-carboxylate

Rendimiento 89.0%

Disolventes

2-propanol

2-propanol

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.DISTILLATIONwas distilled off at 79 to 83° C
2. 2
   workup.DISTILLATIONAfter distilling off 119 g of 2-propanol over 6 hours
3. 3
   workup.ADDITION1.14 g of methyl 3-cyclopropyl-3-oxopropionate was added
4. 4
   workup.ADDITION146 g of toluene was added into the reaction solution
5. 5
   Lavadothe reaction solution was washed with 80 g of 4% aqueous solution of sodium hydroxide
6. 6
   LavadoThe reaction solution was further washed with 25 g of 5% brine solution
7. 7
   Secadodried over 5 g of anhydrous magnesium sulfate
8. 8
   OtroToluene was removed under a reduced pressure, and crystallization

Procedimiento

12 g of methyl 3-cyclopropyl-3-oxopropionate and 25 g of 2-amino-4′-fluorobenzophenone methanesulfonate were added to 146 g of 2-propanol, and 2-propanol was distilled off at 79 to 83° C. After distilling off 119 g of 2-propanol over 6 hours, 1.14 g of methyl 3-cyclopropyl-3-oxopropionate was added and the mixture was heated at 79 to 81° C. for 4 hours. An analysis of the mixture with high performance liquid chromatography (HPLC) showed that the residual amount of 2-amino-4′-fluorobenzophenone as a raw material was 0.9%. 146 g of toluene was added into the reaction solution, and the reaction solution was washed with 80 g of 4% aqueous solution of sodium hydroxide and then 35 g of 2% aqueous solution of sodium hydroxide. The reaction solution was further washed with 25 g of 5% brine solution, and then dried over 5 g of anhydrous magnesium sulfate. Toluene was removed under a reduced pressure, and crystallization was carried out in 180 g of cyclohexane to obtain 22.9 g of methyl 2-cyclopropyl-4-(4′-fluorophenyl)quinoline-3-carboxylate.

Fuente