Hydrochloric Acid → (RS)-Naproxen methyl ester

HRID 1030851Notes

Reaction equation

HRID 1030851 reaction equation
Br[C:2]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH:14]([CH3:18])[C:15]([OH:17])=[O:16])=[CH:7]2.[C:19]1(C)C=C(C)C=C(C)C=1.Cl>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH3:13][O:12][C:11]1[CH:2]=[C:3]2[C:8](=[CH:9][CH:10]=1)[CH:7]=[C:6]([CH:14]([CH3:18])[C:15]([O:17][CH3:19])=[O:16])[CH:5]=[CH:4]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 7947MesityleneHCID 1196952-(5-Bromo-6-methoxynaphthalen-2-yl)propanoic acid

Product 1

HCID 529084(RS)-Naproxen methyl ester

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

16.1 Grams of the methyl ester of the 2-(5-bromo-6-methoxy-2-naphthyl)propionic acid are dissolved in 65 ml of methylene chloride and then 10.4 ml of mesitylene and 12 ml of anhydrous titanium tetrachloride are added while keeping the temperature at about 20° C. The reaction mixture is kept under stirring at room temperature for 80 hours and then is poured into a mixture made of 68 g of crushed ice and of 15 ml of a 35% (w/v) aqueous solution of hydrochloric acid. The layers are separated after 15 minutes of stirring, the aqueous layer is extracted with 30 ml of methylene chloride and then is discarded. The organic layers are collected, first washed with 50 ml of a 1N aqueous solution of hydrochloric acid, then with 50 ml of water and lastly with 50 ml of a 8% (w/v) aqueous solution of sodium bicarbonate. The organic solution is dried over anhydrous sodium sulfate and then is evaporated under vacuum. The residue is crystallized first with n-hexane and then with methyl alcohol obtaining 4 g of product with a yield equal to 32.7%.

Workup

  1. customat about 20° C
  2. additionis poured into a mixture
  3. customThe layers are separated after 15 minutes
  4. stirringof stirring
  5. extractionthe aqueous layer is extracted with 30 ml of methylene chloride
  6. customThe organic layers are collected
  7. washfirst washed with 50 ml of a 1N aqueous solution of hydrochloric acid
  8. dry with materialThe organic solution is dried over anhydrous sodium sulfate
  9. customis evaporated under vacuum
  10. customThe residue is crystallized first with n-hexane

Sources & evidence

ORD record
ord-c4107deb291f45f78864f34a668e7a4f
Source dataset
uspto-grants-1992_04
Patent number
US05107013

Reaction notes

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