Reaction #155427

Reaction equation

4-morpholinecarbonyl chloride

3-fluoro-2-hydroxybenzaldehyde

CH2Cl2

pyridine

→

2-fluoro-6-formylphenyl morpholine-4-carboxylate

Yield 94.1%

Solvents

Water

Conditions

Workup

1. 1
   OtherTo a 250 mL dry round bottom flask
2. 2
   workup.STIRRINGThe mixture was stirred at room temperature for 24 hours
3. 3
   OtherThe CH2Cl2 layer was separated
4. 4
   Extractionthe aqueous layer was extracted continually with CH2Cl2 (100 mL×2)
5. 5
   DryingThe combined CH2Cl2 solution was dried over Na2SO4
6. 6
   OtherAfter removal of the solvent
7. 7
   Otherthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

Procedure

To a 250 mL dry round bottom flask were added 3-fluoro-2-hydroxybenzaldehyde (4.90 g, 35.0 mmol), anhydrous CH2Cl2 (50 mL) and pyridine (3.40 mL, 42.0 mmol). The mixture was stirred in an ice-water bath, then 4-morpholinecarbonyl chloride (4.50 mL, 38.5 mmol) was added. The mixture was stirred at room temperature for 24 hours. Water (80 mL) was added to the reaction mixture. The CH2Cl2 layer was separated, and the aqueous layer was extracted continually with CH2Cl2 (100 mL×2). 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 2-fluoro-6-formylphenyl morpholine-4-carboxylate (8.34 g) as white solid. Yield: 94%. 1H NMR (CDCl3, 300 MHz): δ=10.06 (s, 1H), 7.58 (dt, J=7.8, 1.5 Hz, 1H), 7.39-7.22 (m, 2H), 3.69 (br, 6H), 3.50 (br, 2H). 13C NMR (CDCl3, 75.5 MHz, mixture of two isomers): δ=187.6, 187.5, 170.5, 156.4, 152.4 (d, J=100.7 Hz), 139.9 (d, J=12.8 Hz), 130.5, 126.5 (d, J=7.3 Hz), 125.2 (d, J=3.1 Hz), 121.7 (d, J=17.4 Hz), 66.1, 45.0, 44.3.

Source