Reaction #502114

Reaction equation

1,3-dicyclohexylcarbodiimide

(2S)-2-(6-methoxy(2-naphthyl))propanoic acid

1,3-dihydroxy-acetone

→

title compound

3-Hydroxy-2-oxopropyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Solvents

acetone

acetone

Conditions

Workup

1. 1
   OtherThe byproduct, dicyclohexyl urea was removed by filtration
2. 2
   ConcentrationThe filtrate was concentrated
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2 (150 mL)
4. 4
   Washwashed with 3N HCl (150 mL), water (150 mL×3), brine
5. 5
   Dryingdried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   OtherThe product was separated by silica gel column chromatography
9. 9
   Washeluting with ethyl acetate/hexane (1:2, Rf=0.13)
10. 10
    Otherto obtained

Procedure

A solution of 1,3-dicyclohexylcarbodiimide (2.84 g, 13.8 mmol) in acetone (40 mL) was added, drop-wise, to a solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 3.14 g, 13.6 mmol), 1,3-dihydroxy-acetone (3.11 g, 34.5 mmol) and N,N-dimethylaminopyridine (DMAP,1.4 g, 11.5 mmol) in acetone (100 mL) and stirred at ambient temperature overnight. The byproduct, dicyclohexyl urea was removed by filtration. The filtrate was concentrated and the residue was dissolved in CH2Cl2 (150 mL), washed with 3N HCl (150 mL), water (150 mL×3), brine, and dried over Na2SO4, filtered and concentrated. The product was separated by silica gel column chromatography eluting with ethyl acetate/hexane (1:2, Rf=0.13) to obtained a mixture of the title compound and its dimer. The reaction mixture was treated with ethyl ether and the dimer was removed by filtration. The filtrate was concentrated and dried under vacuum to give the title compound as a sticky oil (1.59 g). The resulted material was use in the next step without further purification. Mass spectrum (API-TIS) m/z 303 (MH)+.

Source