Hydrochloric Acid → Naproxen

HRID 1030852Notes

Reaction equation

HRID 1030852 reaction equation
C1(C)C=C(C)C=C(C)C=1.Br[C:11]1[C:20]([O:21][CH3:22])=[CH:19][CH:18]=[C:17]2[C:12]=1[CH:13]=[CH:14][C:15]([CH:23]([CH3:27])[C:24]([OH:26])=[O:25])=[CH:16]2.[Cl-].[Al+3].[Cl-].[Cl-].Cl>C(Cl)(Cl)Cl>[CH3:27][C@H:23]([C:24]([OH:26])=[O:25])[C:15]1[CH:14]=[CH:13][C:12]2[CH:11]=[C:20]([O:21][CH3:22])[CH:19]=[CH:18][C:17]=2[CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7947MesityleneHCID 1196952-(5-Bromo-6-methoxynaphthalen-2-yl)propanoic acidHCID 6451240Aluminum(III) Chloride

Product 1

HCID 156391NaproxenYield 91.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

20.8 Ml (0.15 moles) of mesitylene and 30.9 g (0.10 moles) of (+)-2-(5-bromo-6-methoxy-2-naphthyl)propionic acid are added to 150 ml of chloroform and the mixture is cooled to 0° C. 20 Grams (0.15 moles) of anhydrous aluminum chloride are added portionwise under strong stirring to the mixture while going on with the cooling so that temperature does not exceed 20° C. The reaction mixture is kept at this temperature for 3 hours and then is poured into a mixture made of 100 g of ice and 10 ml of 32% hydrochloric acid. The reaction mixture is heated to 45° C., the layers are separated, the organic layer is twice washed with 50 ml of 1M hydrochloric acid and then with 100 ml of water. The organic layer is concentrated under vacuum and the residue is crystallized from 75 ml of toluene. The product is filtered and dried obtaining 21 g of the title compound, which corresponds to the drug known as naproxen, having [α]D 20 =+66.5° (C=1% in chloroform), with a yield of 91%.

Workup

  1. customdoes not exceed 20° C
  2. additionis poured into a mixture
  3. temperatureThe reaction mixture is heated to 45° C.
  4. customthe layers are separated
  5. washthe organic layer is twice washed with 50 ml of 1M hydrochloric acid
  6. concentrationThe organic layer is concentrated under vacuum
  7. customthe residue is crystallized from 75 ml of toluene
  8. filtrationThe product is filtered
  9. customdried

Sources & evidence

ORD record
ord-cd5e15b049fb4543841ed0e9f690b31b
Source dataset
uspto-grants-1992_04
Patent number
US05107013

Reaction notes

Loading…