4-Hydroxybenzaldehyde → HCID 58234644, compound

HRID 1877760Notes

Reaction equation

HRID 1877760 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=[O:8])[CH2:3][CH2:2]1.S(Cl)(Cl)=O.N1C=CC=CC=1.O[C:21]1[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[CH:23][CH:22]=1>C(Cl)Cl.O>[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][C:21]2[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[CH:23][CH:22]=2)=[O:8])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 1049PyridineHCID 24386Thionyl ChlorideHCID 219302Oxane-4-carboxylic acid

Product 1

HCID 58234644HCID 58234644, compoundYield 87.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

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.

Workup

  1. customTo a 100 mL dry round bottom flask
  2. temperatureThe mixture was refluxed for 45 minutes
  3. customall the volatile materials were rotary-evaporated
  4. additionTo the residue, anhydrous CH2Cl2 (10 mL) was added
  5. temperaturewarmed from 0° C. to room temperature slowly
  6. customat room temperature
  7. customovernight
  8. customthe CH2Cl2 layer was separated
  9. extractionThe aqueous layer was extracted continually with CH2Cl2 (50 mL×3)
  10. washThe combined CH2Cl2 solution was washed with a cold aqueous solution of saturated NaHCO3 (80 mL)
  11. customAfter drying
  12. customremoval of the solvent
  13. customthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

Sources & evidence

ORD record
ord-18b0ad1723f1478d912588d31a493f6a
Source dataset
uspto-grants-2012_11
Patent number
US08314081B2

Reaction notes

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