Reaction #502115

Reaction equation

1,3-dicyclohexylcarbodiimide

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

2-nitro-2-methyl-1,3-propanediol

→

title compound

3-Hydroxy-2-methyl-2-nitropropyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Solvents

CH2Cl2

THF

Conditions

Workup

1. 1
   OtherThe solvent was evaporated
2. 2
   workup.ADDITIONEtOAc (100 mL) was added to the resulting crude material
3. 3
   Temperaturecooled in a dry-ice bath
4. 4
   Otherthe byproduct, dicyclohexyl urea was removed by filtration
5. 5
   OtherThe product was separated by silica gel column chromatography
6. 6
   Washeluting with ethyl acetate/hexane (1:3, Rf=0.1)

Procedure

A solution of 1,3-dicyclohexylcarbodiimide (4.23 g, 20.5 mmol), (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 4.34 g, 18.9 mmol), and 2-nitro-2-methyl-1,3-propanediol (2.56 g, 19.0 mmol) in CH2Cl2 (50 mL) and THF (50 mL) was stirred at ambient temperature overnight. The solvent was evaporated and EtOAc (100 mL) was added to the resulting crude material, cooled in a dry-ice bath and the byproduct, dicyclohexyl urea was removed by filtration. The product was separated by silica gel column chromatography eluting with ethyl acetate/hexane (1:3, Rf=0.1) to give the title compound (a mixture of diasteromers) as an oil (2.77 g, 42% yield). 1H NMR (300 MHz, CDCl3) δ 7.69-7.60 (m, 3H), 7.34-7.3 (m, 1H), 7.14-7.08 (m, 2H), 4.44 (d, J=4.2 Hz, 2H), 3.86 (s, 3H), 3.85 (q, J=7.2 Hz, 1H), 1.55 (d, J=7.2 Hz, 3H), 1.36 & 1.40 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 174.14, 174.02 157.57, 134.53, 134.51, 133.64, 129.13, 128.7, 127.17, 125.87, 125.84, 119.0, 105.47, 89.53, 89.42, 64.67, 64.52, 64.19, 55.12, 45.04, 18.25, 18.03, 17.82, 17.79. Mass spectrum (API-TIS) m/z 348 (MH)−.

Source