4-Methyloxybenzyl chloride → 5-(benzylsulfanyl)-3-(methoxymethoxy)-1-(methoxymethyl)pyridin-2(1H)-one

HRID 709054Notes

Reaction equation

HRID 709054 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[C:10](=[O:11])[N:9]([CH2:12][O:13][CH3:14])[CH:8]=[C:7]([S:15][CH2:16][CH2:17][C:18](OC)=O)[CH:6]=1.CC(C)([O-])C.[K+].Cl[CH2:29][C:30]1C=CC(OC)=[CH:32][CH:31]=1>C1COCC1>[CH2:16]([S:15][C:7]1[CH:6]=[C:5]([O:4][CH2:3][O:2][CH3:1])[C:10](=[O:11])[N:9]([CH2:12][O:13][CH3:14])[CH:8]=1)[C:17]1[CH:18]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 699934-Methyloxybenzyl chlorideHCID 23665647Potassium tert-butoxideHCID 86731526Methyl 3-((5-(methoxymethoxy)-1-(methoxymethyl)-6-oxo-1,6-dihydropyridin-3-yl)thio)propanoate2×

Product 1

HCID 867315415-(benzylsulfanyl)-3-(methoxymethoxy)-1-(methoxymethyl)pyridin-2(1H)-oneYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 3-{[5-(methoxymethoxy)-1-(methoxymethyl)-6-oxo-1,6-dihydropyridin-3-yl]sulfanyl}propanoate (Intermediate 16; 300 mg, 0.95 mmol) in THF (5 ml) was cooled to −45° C. and potassium tert-butoxide (117 mg, 0.10 mmol) was added. After stirring at this temperature for 1 hour 1-(chloromethyl)-4-methoxybenzene (154 ml, 1134 mmol) was added and the reaction stirred for 16 hours. The reaction mixture was partitioned between dichloromethane and water. The aqueous layer was re-extracted and the combined organics dried and concentrated under reduced pressure. The resultant residue was purified by column chromatography (SiO2: 80-100% ethyl acetate/petrol) to yield 5-(benzylsulfanyl)-3-(methoxymethoxy)-1-(methoxymethyl)pyridin-2(1H)-one (251 mg, 83%).

Workup

  1. additionwas added
  2. customThe reaction mixture was partitioned between dichloromethane and water
  3. extractionThe aqueous layer was re-extracted
  4. customthe combined organics dried
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by column chromatography (SiO2: 80-100% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-dd9e5ec4f33749aa9dc89ff2f7c244b5
Source dataset
uspto-grants-2015_11
Patent number
US09180122B2

Reaction notes

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