Sodium hydride → HCID 58306504, compound

HRID 1909873Notes

Reaction equation

HRID 1909873 reaction equation
[OH:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br-].[Li+].[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Br)=[CH:19][CH:18]=1>O.CN(C=O)C.COCCOC>[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][N:7]2[C:2](=[O:1])[CH:3]=[CH:4][CH:5]=[C:6]2[C:8]([O:10][CH3:11])=[O:9])=[CH:19][CH:18]=1.[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][O:1][C:2]2[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=2)=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 82050Lithium BromideHCID 178497975HCID 178497975, compound

Product 2

HCID 58306504HCID 58306504, compoundHCID 58306546HCID 58306546, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of ice-cooled methyl 6-hydroxypyridine-2-carboxylate (800 mg), DME (10.5 mL), and DMF (2.6 mL) was added sodium hydride (55% oil dispersion, 240 mg), followed by stirring for 10 minutes. To this was added lithium bromide (910 mg), and then the mixture was stirred at room temperature for 15 minutes and further 4-chlorobenzylbromide (2.15 g) was added thereto. This mixture was stirred at 65° C. for 20 hours. Water was added thereto, followed by extraction with ethyl acetate-diethyl ether, and the organic layer was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain methyl 1-(4-chlorobenzyl)-6-oxo-1,6-dihydropyridine-2-carboxylate (270 mg; Example 41a) and methyl 6-[(4-chlorobenzyl)oxy]pyridine-2-carboxylate (448 mg; Example 41b), as a colorless oily substance, respectively.

Workup

  1. additionTo a mixture of ice-
  2. stirringthe mixture was stirred at room temperature for 15 minutes
  3. stirringThis mixture was stirred at 65° C. for 20 hours
  4. extractionfollowed by extraction with ethyl acetate-diethyl ether
  5. washthe organic layer was washed with water and saturated brine in this order
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customthe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-a477b5d8112440a091cdac3a7e1436d9
Source dataset
uspto-grants-2013_12
Patent number
US08598355B2

Reaction notes

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