Methanol → 1-(2-Chloro-4-pyridyl)-3-hydroxymethyl-6,7-diethoxynaphthalene

HRID 324027Notes

Reaction equation

HRID 324027 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([O:21][CH2:22][CH3:23])=[C:15]([O:18][CH2:19][CH3:20])[CH:16]=3)[CH:11]=[C:10]([C:24](O)=[O:25])[CH:9]=2)[CH:5]=[CH:4][N:3]=1.CO.[OH-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([O:21][CH2:22][CH3:23])=[C:15]([O:18][CH2:19][CH3:20])[CH:16]=3)[CH:11]=[C:10]([CH2:24][OH:25])[CH:9]=2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 220073981-(2-Chloro-4-pyridyl)-3-carboxy-6,7-diethoxynaphthalene

Product 1

HCID 220073461-(2-Chloro-4-pyridyl)-3-hydroxymethyl-6,7-diethoxynaphthalene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a suspension of 1-(2-chloro-4-pyridyl)-3-carboxy-6,7-diethoxynaphthalene in tetrahydrofuran (50 ml) is added dropwise a solution of 70% sodium aluminum bis(2-methoxyethoxy) hydride (70% toluene solution, 29.4 ml) in tetrahydrofuran (50 ml) at a temperature below 5° C. under nitrogen atmosphere, and the mixture is reacted at the same temperature for one hour. After the reaction is complete, to the mixture is added methanol (12 ml), and further thereto is added a 6.25 M aqueous sodium hydroxide solution (48 ml), and the mixture is stirred at 50° C. for one hour. The tetrahydrofuran layer is separated from the mixture, and the aqueous solution is extracted with methylene chloride, and the methylene chloride layer is separated, and combined with the tetrahydrofuran layer, then concentrated under reduced pressure. The resultant is extracted again with methylene chloride, washed, dried, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent; chloroform:ethyl acetate=4:1), and crystallized from ether to give 1-(2-chloro-4-pyridyl)-3-hydroxymethyl-6,7-diethoxynaphthalene (3.94 g).

Workup

  1. customthe mixture is reacted at the same temperature for one hour
  2. customThe tetrahydrofuran layer is separated from the mixture
  3. extractionthe aqueous solution is extracted with methylene chloride
  4. customthe methylene chloride layer is separated
  5. concentrationconcentrated under reduced pressure
  6. extractionThe resultant is extracted again with methylene chloride
  7. washwashed
  8. customdried
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by silica gel column chromatography (solvent; chloroform:ethyl acetate=4:1)
  11. customcrystallized from ether

Sources & evidence

ORD record
ord-d1bbeb2c0d4147adab5db1b2340660db
Source dataset
uspto-grants-2001_04
Patent number
US06214996B1

Reaction notes

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