Ammonium Chloride → 2-Benzyloxy-4,6-dimethylpyridin-3-yl 4-(2-methoxymethyloxyethyl)phenyl methanol

HRID 916579Notes

Reaction equation

HRID 916579 reaction equation
[CH3:1][O:2][CH2:3][O:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][CH:8]=1.C([Li])(C)(C)C.[CH2:19]([O:26][C:27]1[C:32]([CH:33]=[O:34])=[C:31]([CH3:35])[CH:30]=[C:29]([CH3:36])[N:28]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:19]([O:26][C:27]1[C:32]([CH:33]([C:10]2[CH:11]=[CH:12][C:7]([CH2:6][CH2:5][O:4][CH2:3][O:2][CH3:1])=[CH:8][CH:9]=2)[OH:34])=[C:31]([CH3:35])[CH:30]=[C:29]([CH3:36])[N:28]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 155094031-Bromo-4-[2-(methoxymethoxy)ethyl]benzeneHCID 229349822-(Benzyloxy)-4,6-dimethylnicotinaldehydeHCID 178418306HCID 178418306, compound

Product 1

HCID 694217802-Benzyloxy-4,6-dimethylpyridin-3-yl 4-(2-methoxymethyloxyethyl)phenyl methanolYield 89.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(2-methoxymethyloxyethyl) bromobenzene (0.60 g) in tetrahydrofuran (6 mL) was added tert-butyllithium (1.5 mol/L solution in hexane, 2.0 mL) at −78° C. under an argon atmosphere, and the mixture was stirred for 30 minutes. Then, a solution of 2-benzyloxy-3-formyl-4,6-dimethylpyridine (0.49 g) in tetrahydrofuran (5 mL) was added to the reaction mixture, and the mixture was stirred for 3 hours at 0° C. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with dimethyl ether. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=5/1) to give 2-benzyloxy-4,6-dimethylpyridin-3-yl 4-(2-methoxymethyloxyethyl)phenyl methanol (0.74 g). To a solution of the obtained 2-benzyloxy-4,6-dimethylpyridin-3-yl 4-(2-methoxymethyloxyethyl)phenyl methanol (0.11 g) in ethanol (5.3 mL) was added 10% palladium carbon powder (0.065 g), and the mixture was stirred for 11 hours at room temperature under a hydrogen atmosphere. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography on silica gel (developing solvent: dichloro-methane/methanol=10/1) to give 3-[4-(2-methoxymethyloxy-ethyl)benzyl]-4,6-dimethyl-1H-pyridin-2-one (0.074 g).

Workup

  1. stirringthe mixture was stirred for 3 hours at 0° C
  2. extractionthe mixture was extracted with dimethyl ether
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=5/1)

Sources & evidence

ORD record
ord-8c334b64b91c4e749f99fe3e4ae7010f
Source dataset
uspto-grants-2007_09
Patent number
US07271153B2

Reaction notes

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