Reaction #84569

Reaction equation

N-(3-chloro-4-morpholinophenyl)-3-oxobutanamide

2-((4-chloronaphthalen-1-yl)oxy)acetamide

toluene

NH4Cl

→

title compound

Yield 56.4%

3-(3-chloro-4-morpholinophenyl)-2-(((4-chloronaphthalen-1-yl)oxy)methyl)-6-methylpyrimidin-4(3H)-one

Yield 56.4%

Solvents

xylene

Conditions

Workup

1. 1
   TemperatureThe mixture was cooled to rt
2. 2
   workup.STIRRINGThe resulting mixture was stirred at rt overnight
3. 3
   Filtrationfiltered
4. 4
   Extractionthe filtrate was extracted with DCM (20 mL×4)
5. 5
   WashThe combined organic layers were washed with brine (30 mL×2)
6. 6
   Dryingdried over anhydrous Na2SO4
7. 7
   Concentrationconcentrated in vacuo
8. 8
   OtherThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1)

Procedure

A mixture of N-(3-chloro-4-morpholinophenyl)-3-oxobutanamide (0.59 g, 2.0 mmol), 2-((4-chloronaphthalen-1-yl)oxy)acetamide (0.94 g, 4.0 mmol) and titanium tetraisopropanolate (4.8 mL) in xylene (10 mL) was stirred at 165° C. for 24 h. The mixture was cooled to rt and 60 mL of toluene and 60 mL of saturated NH4Cl aqueous solution were added. The resulting mixture was stirred at rt overnight and filtered and the filtrate was extracted with DCM (20 mL×4). The combined organic layers were washed with brine (30 mL×2), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:1) to give the title compound as a yellow solid (0.56 g, 56%). The compound was characterized by the following spectroscopic data:

Source