Reaction #4500

Reaction equation

NaNO2

4-[2-Hydroxy-2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]aniline

HBr

methyl acrylate

→

methyl 2-bromo-3-{4-[2-hydroxy-2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy] phenyl}propionate

Solvents

water

methanol

acetone

Conditions

Workup

1. 1
   workup.ADDITIONwas added to the solution
2. 2
   Temperatureby warming at 38° C
3. 3
   workup.STIRRINGstirring
4. 4
   ConcentrationAfter concentration
5. 5
   Extractionextracted with ethyl acetate
6. 6
   WashThe ethyl acetate layer was washed with water
7. 7
   Dryingdried (MgSO4)
8. 8
   Concentrationconcentrated

Procedure

4-[2-Hydroxy-2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]aniline (18.5 g) was dissolved in methanol (50 ml)-acetone (150 ml), and 47% aqueous HBr (41.0 g) was added to the solution. Then, a solution of NaNO2 (4.5 g) in water (10 ml) was added dropwise to the mixture at a temperature of not higher than 5° C. The whole was stirred at 5° C. for 15 minutes, and methyl acrylate (30.4 g) was added to the mixed solution, followed by warming at 38° C. Cuprous oxide (2.0 g) was added in small portions to the reaction solution with vigorous stirring, and stirring was continued until evolution of nitrogen gas stopped. After concentration, the residue was made basic with aqueous ammonia, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4) concentrated to give methyl 2-bromo-3-{4-[2-hydroxy-2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy] phenyl}propionate as a crude oily material (27.0 g, 98.5%). IR (Neat) cm-1 : 3300, 1735. NMR δ (ppm) in CDCl3 : 2.40(3H, s), 3.0(1H, broad), 3.11(1H, d.d, J=14 and 7 Hz), 3.39(1H, d.d, J=14 and 7 Hz), 3.68(3H, s), 4.0 to 4.5(3H, m), 5.05(1H, d.d, J=8 and 5 Hz), 6.0 to 7.2(4H, m), 7.4 (3H, m), 7.9(2H, m).

Source