تفاعل #155425

معادلة التفاعل

2,6-difluoro-4-hydroxybenzaldehyde

pyridine

4-morpholinecarbonyl chloride

→

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

المردود 94.0%

المذيبات

CH2Cl2

Water

CH2Cl2

ظروف التفاعل

المعالجة

1. 1
   أخرىTo 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
   أخرىThe CH2Cl2 layer was separated
5. 5
   استخلاصthe aqueous layer was extracted continually with CH2Cl2 (50 mL×3)
6. 6
   تجفيفThe combined CH2Cl2 solution was dried over Na2SO4
7. 7
   أخرىAfter removal of the solvent
8. 8
   أخرىthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

الإجراء التجريبي

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.

المصدر