Reaction #1328446

Reaction equation

isoamyl nitrite

ethyl 2-[3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]propionate

hydrochloric acid

→

ethyl 2-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3, 6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]propionate

Solvents

acetonitrile

acetonitrile

Conditions

Workup

1. 1
   Extractionthe mixture was extracted with ethyl acetate
2. 2
   WashThe organic layer was washed with saturated aqueous sodium chloride solution
3. 3
   Dryingdried over anhydrous magnesium sulfate
4. 4
   Concentrationconcentrated

Procedure

A solution of 10.99 g of isoamyl nitrite in 10 ml of acetonitrile was added to a mixture of 15.46 g of ethyl 2-[3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]propionate, 6.19 g of copper(I) chloride, 12.61 g of copper(II) chloride, and 120 ml of acetonitrile at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was poured into a mixture of ice and hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 13.16 g of ethyl 2-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3, 6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]propionate (compound b-10).

Source