Hydrochloric Acid → 4-[4-(2-Benzoyloxyethyl)benzyl]-3-hydroxypyridine

HRID 916593Notes

Reaction equation

HRID 916593 reaction equation
[C:1]([O:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([C:20]2[CH:25]=[CH:24][N:23]=[CH:22][C:21]=2[O:26]COC)O)=[CH:14][CH:13]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>C(O)C>[C:1]([O:9][CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][C:20]2[CH:25]=[CH:24][N:23]=[CH:22][C:21]=2[OH:26])=[CH:16][CH:17]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 22934986HCID 22934986, compound

Product 1

HCID 692201914-[4-(2-Benzoyloxyethyl)benzyl]-3-hydroxypyridine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-(2-benzoyloxyethyl)benzyl alcohol (1.2 g) in dichloromethane (50 mL) was added manganese dioxide (12 g), and the mixture was stirred for 23 hours at room temperature. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure to give 4-(2-benzoyloxyethyl)benzaldehyde (0.87 g). To a solution of 3-(methoxymethyloxy)pyridine (0.20 g) in diethyl ether (20 mL) was added tert-butyllithium (1.51 mol/L solution in pentane, 1.2 mL) at −78° C., and the mixture was stirred for 30 minutes. To the reaction mixture was added a solution of 4-(2-benzoyloxy-ethyl)benzaldehyde (0.44 g) in diethyl ether (4 mL). The temperature was raised to room temperature, and the mixture was stirred for 1 hour. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. To the residue were added hexane and ethyl acetate, and the resulting crystals were collected by filtration and dried under reduced pressure to give 4-(2-benzoyloxyethyl)phenyl-3-(methoxymethyloxy)pyridin-4-yl-methanol (0.30 g). To a solution of the obtained 4-(2-benzoyloxyethyl)phenyl-3-(methoxymethyloxy)pyridin-4-yl-methanol (0.28 g) in ethanol (4.8 mL) was added concentrated hydrochloric acid (0.6 mL), and the mixture was heated under reflux for 10 minutes. The solvent of the reaction mixture was removed under reduced pressure, and ethyl acetate was added to the residue. The resulting precipitated crystals were collected by filtration and dried to give4-(2-benzoyloxyethyl)-phenyl-3-hydroxypyridin-4-ylmethanol hydrochloride (0.28 g). To a solution of the obtained 4-(2-benzoyloxyethyl)phenyl-3-hydroxypyridin-4-ylmethanol hydrochloride (0.27 g) in ethanol (6.9 mL) was added 10% palladium carbon powder (0.27 g), and the mixture was stirred for 3.5 hours at room temperature under a hydrogen atmosphere. The insoluble material was removed by filtration, and the solvent of the filtrate was removed under reduced pressure. To the residue were added ethyl acetate and diethyl ether, and the resulting crystals were collected by filtration. To the obtained crystals was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. After the organic layer was washed with brine and dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. To the residue was added diethyl ether, and the resulting precipitated crystals were collected by filtration and dried under reduced pressure to give 4-[4-(2-benzoyloxyethyl)benzyl]-3-hydroxypyridine (0.12. g).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 10 minutes
  3. customThe solvent of the reaction mixture was removed under reduced pressure, and ethyl acetate
  4. additionwas added to the residue
  5. customThe resulting precipitated crystals
  6. filtrationwere collected by filtration
  7. dry with materialdried to give4-(2-benzoyloxyethyl)-phenyl-3-hydroxypyridin-4-ylmethanol hydrochloride (0.28 g)
  8. additionTo a solution of the obtained 4-(2-benzoyloxyethyl)phenyl-3-hydroxypyridin-4-ylmethanol hydrochloride (0.27 g) in ethanol (6.9 mL) was added 10% palladium carbon powder (0.27 g)
  9. customThe insoluble material was removed by filtration
  10. customthe solvent of the filtrate was removed under reduced pressure
  11. additionTo the residue were added ethyl acetate and diethyl ether
  12. filtrationthe resulting crystals were collected by filtration
  13. additionTo the obtained crystals was added saturated aqueous sodium bicarbonate solution
  14. extractionthe mixture was extracted with ethyl acetate
  15. washAfter the organic layer was washed with brine
  16. dry with materialdried over anhydrous sodium sulfate
  17. customthe solvent was removed under reduced pressure
  18. additionTo the residue was added diethyl ether
  19. customthe resulting precipitated crystals
  20. filtrationwere collected by filtration
  21. customdried under reduced pressure

Sources & evidence

ORD record
ord-13befa75e8104363a14d8451a111fbd9
Source dataset
uspto-grants-2007_09
Patent number
US07271153B2

Reaction notes

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