Reaction #155422

Reaction equation

4-hydroxybenzaldehyde

tetrahydro-pyran-4-carboxylic acid

thionyl chloride

pyridine

→

4-formylphenyl tetrahydro-2H-pyran-4-carboxylate

Yield 87.4%

Solvents

water

CH2Cl2

Conditions

Workup

1. 1
   OtherTo a 100 mL dry round bottom flask
2. 2
   TemperatureThe mixture was refluxed for 45 minutes
3. 3
   Otherall the volatile materials were rotary-evaporated
4. 4
   workup.ADDITIONTo the residue, anhydrous CH2Cl2 (10 mL) was added
5. 5
   Temperaturewarmed from 0° C. to room temperature slowly
6. 6
   Otherat room temperature
7. 7
   Otherovernight
8. 8
   Otherthe CH2Cl2 layer was separated
9. 9
   ExtractionThe aqueous layer was extracted continually with CH2Cl2 (50 mL×3)
10. 10
    WashThe combined CH2Cl2 solution was washed with a cold aqueous solution of saturated NaHCO3 (80 mL)
11. 11
    OtherAfter drying
12. 12
    Otherremoval of the solvent
13. 13
    Otherthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

Procedure

To a 100 mL dry round bottom flask were added tetrahydro-pyran-4-carboxylic acid (2.8 g, 21.5 mmol), thionyl chloride (2.8 mL, 34.4 mmol). The mixture was refluxed for 45 minutes, then all the volatile materials were rotary-evaporated. To the residue, anhydrous CH2Cl2 (10 mL) was added. The resulting solution was cooled to 0° C., and pyridine (2.63 g, 21.5 mmol) was added, followed by a solution of 4-hydroxybenzaldehyde (2.04 g, 25.8 mmol) in anhydrous CH2Cl2 (30 mL). The reaction mixture was stirred and warmed from 0° C. to room temperature slowly, then at room temperature overnight. To the reaction mixture, water (60 mL) was added and the CH2Cl2 layer was separated. The aqueous layer was extracted continually with CH2Cl2 (50 mL×3). The combined CH2Cl2 solution was washed with a cold aqueous solution of saturated NaHCO3 (80 mL). After drying and removal of the solvent, the residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting) to give 4-formylphenyl tetrahydro-2H-pyran-4-carboxylate (4.40 g) as colorless oil. Yield: 87%. 1H NMR (CDCl3, 300 MHz): δ=9.97 (s, 1H), 7.91 (d, J=8.7 Hz, 2H), 7.27 (d, J=8.4 Hz, 2H), 4.06-4.00 (m, 2H), 3.55-3.47 (m, 2H), 2.88-2.81 (m, 1H), 2.03-1.88 (m, 4H). 13C NMR (CDCl3, 75.5 MHz): δ=190.9, 172.2, 155.3, 133.9, 131.1, 122.2, 115.9, 66.8, 40.1, 28.4.

Source