Dimethyl Sulfate → 3-Methoxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one

HRID 2268141Notes

Reaction equation

HRID 2268141 reaction equation
[OH:1][C:2]1[C:3](=[O:21])[N:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH2:5][CH2:6][C:7]=1[C:8](=[O:11])[CH2:9][CH3:10].[C:22](=O)([O-])[O-].[Cs+].[Cs+].S(OC)(OC)(=O)=O>CN(C)C=O>[CH3:22][O:1][C:2]1[C:3](=[O:21])[N:4]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[CH2:5][CH2:6][C:7]=1[C:8](=[O:11])[CH2:9][CH3:10]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 10796Cesium carbonateHCID 12037815AGN-PC-0NHKTJ

Product 1

HCID 111974373-Methoxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-Hydroxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one (17.35 kg, 60 moles) and cesium carbonate (22.126 kg, 67.9 moles) were added to dry dimethylformamide (24 gal, 90.8 L) in a clean, dry 100 gallon tank. The suspension was stirred a half hour to insure dispersion. Dimethyl sulfate (8.552 kg, 67.8 moles) was added neat over a period of 30 minutes keeping the temperature 20-25° C. When the charge was complete the addition funnel was rinsed into the tank with additional DMF (500 ml). The reaction was allowed to stir at 20-25° C. for 16 hours. The reaction was diluted with ethyl acetate (108 gal, 408.8 L) and was washed with water (4×22 gal (83.3 L)). The ethyl acetate solution was washed with a solution made up of 6.94 liters 50% sodium hydroxide in 22 gal (83.3 L) of water followed by washing with a solution made up with 6.94 liters of concentrated HCl in 22 gal (83.3 L) of water. The organic solution was dried by washing with brine (14 gal, 53 L) The ethyl acetate was vacuum stripped to an oil which was suitable for use in the next step. The estimated yield based on NMR analysis of residual solvent was 89%. A small sample was isolated for characterization.

Workup

  1. customdry 100 gallon tank
  2. customthe temperature 20-25° C
  3. washwas rinsed into the tank with additional DMF (500 ml)
  4. stirringto stir at 20-25° C. for 16 hours
  5. additionThe reaction was diluted with ethyl acetate (108 gal, 408.8 L)
  6. washwas washed with water (4×22 gal (83.3 L))
  7. washThe ethyl acetate solution was washed with a solution
  8. washby washing with a solution
  9. customThe organic solution was dried
  10. washby washing with brine (14 gal, 53 L) The ethyl acetate
  11. customThe estimated yield
  12. customA small sample was isolated for characterization

Sources & evidence

ORD record
ord-cabe13ad15b74ad68ae139896f94d395
Source dataset
uspto-grants-2001_12
Patent number
US06326495B2

Reaction notes

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