Ethanol → 2-Ethyl-3-hydroxy-1-[2-(alpha-methylpropionyloxy)ethyl]pyridin-4-one

HRID 374449Notes

Reaction equation

HRID 374449 reaction equation
Cl.C([O:9][C:10]1[C:15](=[O:16])[CH:14]=[CH:13][N:12]([CH2:17][CH2:18][OH:19])[C:11]=1[CH2:20][CH3:21])C1C=CC=CC=1.C(N(CC)CC)C.[C:29](Cl)(=[O:33])[CH:30]([CH3:32])[CH3:31].CCO>CN(C)C=O.CCOC(C)=O>[CH2:20]([C:11]1[N:12]([CH2:17][CH2:18][O:19][C:29](=[O:33])[CH:30]([CH3:32])[CH3:31])[CH:13]=[CH:14][C:15](=[O:16])[C:10]=1[OH:9])[CH3:21]

Participants

7

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 189971673-Benzyloxy-2-ethyl-1-(2-hydroxyethyl)pyridin-4-one hydrochloride

Product 1

HCID 97949942-Ethyl-3-hydroxy-1-[2-(alpha-methylpropionyloxy)ethyl]pyridin-4-oneYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-benzyloxy-2-ethyl-1-(2-hydroxyethyl)pyridin-4-one hydrochloride (3.1 g, 0.01 mole; prepared as described in Example 2) in 100 ml of dry dimethylformamide was added dropwise triethylamine (7 ml, 0.05 mole) whilst stirring over 15 minutes under N2. Isobutyryl chloride (4.2 ml, 0.04 mole) was then added dropwise and the mixture was heated at 75°-78° C. overnight under N2. The reaction was monitored by tlc (silica; 50% EtOH:50% EtOAc) and after filtration the dimethylformamide was removed under high vacuum by rotary evaporation. The solid residue was dissolved in 100 ml of dichloromethane and washed with 5% w/v aqueous NaHCO3 (3×100 ml) and water (2×100 ml). The organic layer was dried over Na2SO4, filtered and rotary evaporated to give a crude solid. Purification was achieved by recrystallization using activated charcoal in ethyl acetate. The filtrate was used for further crystallization of the solid from ethyl acetate to give the title compound in 40% yield, δ(DMSO): 0.8-1.12 (15H, m), 2.3-2.8 (4H, m), 4.15 (4H, s), 5.9-6.1 (1H, d, 7 Hz), 7.5-7.7 (1H, d, 8 Hz).

Workup

  1. temperaturethe mixture was heated at 75°-78° C. overnight under N2
  2. filtrationafter filtration the dimethylformamide
  3. customwas removed under high vacuum by rotary evaporation
  4. dissolutionThe solid residue was dissolved in 100 ml of dichloromethane
  5. washwashed with 5% w/v aqueous NaHCO3 (3×100 ml) and water (2×100 ml)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. customrotary evaporated
  9. customto give a crude solid
  10. customPurification
  11. customwas achieved by recrystallization
  12. customThe filtrate was used for further crystallization of the solid from ethyl acetate

Sources & evidence

ORD record
ord-a4da851c14a74098bb5e2caf7ba51835
Source dataset
uspto-grants-1996_01
Patent number
US05480894

Reaction notes

Loading…