Benzyl Chloride → alpha-Methyl-6-(phenylmethoxy)-2-naphthaleneacetic acid

HRID 1655556Notes

Reaction equation

HRID 1655556 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([CH:12]([CH3:16])[C:13]([OH:15])=[O:14])[CH:6]=[CH:5]2.C[O-].[Na+].[CH2:20](Cl)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CO>[CH3:16][CH:12]([C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([O:1][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:3]=2)[CH:8]=1)[C:13]([OH:15])=[O:14]

Participants

5

Reactant 3

HCID 7503Benzyl ChlorideHCID 162920DesmethylnaproxenHCID 10942334Sodium Methoxide

Product 1

HCID 15030177alpha-Methyl-6-(phenylmethoxy)-2-naphthaleneacetic acidYield 38.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 6-hydroxy-α-methyl-2-naphthaleneacetic acid (6.48 g, 30 mmol) in methanol (100 ml) is added sodium methoxide (60 mm). After 10 minutes the solvent is removed and replaced with dimethylformamide (100 ml). Benzyl chloride (7.6 g, 60 mmol) is then added and the reaction mixture is stirred overnight at room temperature. The reaction is then heated at 150° C. for 1 hour. The solvent is then removed and the residue is partitioned between water and methylene chloride. The organic layer is washed with water, dried over magnesium sulfate and evaporated to 11.5 g of crude product. This crude product is extracted with 100 ml hot hexane which affords 3.5 g of white crystals. A final recrystallization from methanol affords 2.5 g of white crystals of the intermediate ethyl ester (21 % yield, m.p. 76°-78° C.).

Workup

  1. customAfter 10 minutes the solvent is removed
  2. temperatureThe reaction is then heated at 150° C. for 1 hour
  3. customThe solvent is then removed
  4. customthe residue is partitioned between water and methylene chloride
  5. washThe organic layer is washed with water
  6. dry with materialdried over magnesium sulfate
  7. customevaporated to 11.5 g of crude product
  8. extractionThis crude product is extracted with 100 ml hot hexane which

Sources & evidence

ORD record
ord-5edeee84d4e44fe680c60ee24b500443
Source dataset
uspto-grants-1993_10
Patent number
US05250693

Reaction notes

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