Reacción #155425

Ecuación de reacción

2,6-difluoro-4-hydroxybenzaldehyde

pyridine

4-morpholinecarbonyl chloride

→

3,5-difluoro-4-formylphenyl morpholine-4-carboxylate

Rendimiento 94.0%

Disolventes

CH2Cl2

Water

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroTo a 250 mL dry round bottom flask
2. 2
   workup.STIRRINGAfter stirring at 0° C. for 1 hour
3. 3
   workup.STIRRINGthe mixture was stirred at room temperature overnight
4. 4
   OtroThe CH2Cl2 layer was separated
5. 5
   Extracciónthe aqueous layer was extracted continually with CH2Cl2 (50 mL×3)
6. 6
   SecadoThe combined CH2Cl2 solution was dried over Na2SO4
7. 7
   OtroAfter removal of the solvent
8. 8
   Otrothe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

Procedimiento

To a 250 mL dry round bottom flask were added 2,6-difluoro-4-hydroxybenzaldehyde (5.53 g, 35.0 mmol), anhydrous CH2Cl2 (40 mL) and pyridine (3.68 mL, 45.5 mmol). The mixture was stirred in an ice-water bath, then 4-morpholinecarbonyl chloride (4.4 mL, 37.4 mmol) was added. After stirring at 0° C. for 1 hour, the mixture was stirred at room temperature overnight. Water (80 mL) and CH2Cl2 (50 mL) were added to the reaction mixture. The CH2Cl2 layer was separated, and the aqueous layer was extracted continually with CH2Cl2 (50 mL×3). The combined CH2Cl2 solution was dried over Na2SO4. After removal of the solvent, the residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting) to give 3,5-difluoro-4-formylphenyl morpholine-4-carboxylate (8.90 g) as white solid. Yield: 94%. 1H NMR (CDCl3, 300 MHz): δ=10.28 (s, 1H), 6.91 (dd, J=10.8, 1.5 Hz, 2H), 3.77-3.58 (m, 8H). 13C NMR (CDCl3, 75.5 MHz, mixture of two isomers): δ=183.7, 163.8 (dd, J=263.1, 8.53 Hz), 157.0 (t, J=15.3 Hz), 151.8, 111.7 (t, J=11.5 Hz), 106.6 (dd, J=25.1, 3.70 Hz), 66.6, 66.5, 45.2, 44.5.

Fuente