Hydrochloric Acid → 6-Hydroxymethyl-3,4-bis[(p-methoxybenzyl)oxy]-pyridine

HRID 627113Notes

Reaction equation

HRID 627113 reaction equation
[OH:1][CH2:2][C:3]1[NH:4][CH:5]=[C:6]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[C:7](=[O:9])[CH:8]=1.[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26]Cl)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O>[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][O:9][C:7]2[C:6]([O:10][CH2:11][C:12]3[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)=[CH:5][N:4]=[C:3]([CH2:2][OH:1])[CH:8]=2)=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 151595322-(Hydroxymethyl)-5-[(4-methoxyphenyl)methoxy]pyridin-4(1H)-one2×

Product 1

HCID 156625066-Hydroxymethyl-3,4-bis[(p-methoxybenzyl)oxy]-pyridineYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(hydroxymethyl)-5-(4-methoxybenzyloxy)pyridin-4(1H)-one (Intermediate 62, 3.48 g, 13.32 mmol) in DMF (100 mL) at room temperature was added 4-methoxybenzyl chloride (1.987 mL, 14.65 mmol) followed by potassium carbonate (2.273 mL, 39.96 mmol). The reaction mixture was stirred for 1 hour at room temperature then heated at 80° C. for 1.5 hours. The reaction mixture was cooled to room temperature, poured into water and extracted twice with ethyl acetate. The combined extracts were washed with water and brine. The ethyl acetate layer was concentrated to afford an oil. To the oil was added 1N HCl and a light brown solid crashed out. This was collected by filtration. The solid was taken up in ethyl acetate and washed with saturated sodium bicarbonate. The organics were dried over magnesium sulfate, filtered and concentrated to afford the title compound as a brown solid (2.62 g, 52%).

Workup

  1. temperaturethen heated at 80° C. for 1.5 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted twice with ethyl acetate
  4. washThe combined extracts were washed with water and brine
  5. concentrationThe ethyl acetate layer was concentrated
  6. customto afford an oil
  7. filtrationThis was collected by filtration
  8. washwashed with saturated sodium bicarbonate
  9. dry with materialThe organics were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-a3a171704dc8425e8667644eb6c46fbf
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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