Reaction #502128

Reaction equation

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

(R)-(+)-3-benzyloxy-1,2-propanediol

1,3-dicyclohexylcarbodiimide

→

(2R)-2-hydroxy-3-(phenylmethoxy)propyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Solvents

CH2Cl2

Conditions

Workup

1. 1
   OtherThe byproduct, dicyclohexyl urea, was removed by filtration
2. 2
   OtherThe reaction mixture was partitioned between HCl (3N, 50 mL) and CH2Cl2 (50 mL×2)
3. 3
   WashThe combined organic extracts were back washed with water, brine
4. 4
   Dryingdried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   Otherdried under vacuum
8. 8
   OtherThe product was separated by silica gel column chromatography
9. 9
   Washeluting with EtOAc:hexane (1:2, Rf=0.23)
10. 10
    Otherto give

Procedure

A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 3.70 g, 16.1 mmol), (R)-(+)-3-benzyloxy-1,2-propanediol (2.92 g, 19.0 mmol), N,N-dimethylaminopyridine (DMAP, 0.40 g, 3.3 mmol) and 1,3-dicyclohexylcarbodiimide (3.61 g, 17.5 mmol) in CH2Cl2 (120 mL) was stirred at ambient temperature overnight. The byproduct, dicyclohexyl urea, was removed by filtration. The reaction mixture was partitioned between HCl (3N, 50 mL) and CH2Cl2 (50 mL×2). The combined organic extracts were back washed with water, brine, dried over Na2SO4, filtered, concentrated and dried under vacuum. The product was separated by silica gel column chromatography eluting with EtOAc:hexane (1:2, Rf=0.23) to give a mixture of the 1- and 2-glycerol ester isomers (88:12, 3.87 g). 1H NMR (300 MHz, CDCl3) δ 7.69-7.64 (m, 3H), 7.40-7.03 (m, 8H), 5.34 (s, 2H), 4.17-4.14 (m, 2H), 3.88 (s, 3H), 3.9-3.85 (m, 2H), 3.33-3.28 (m, 2H), 2.45 (br. d, 1H), 1.56 (d, J=7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 174.6, 157.6, 137.6, 135.4, 133.6, 129.6, 129.2, 128.8, 128.3, 127.7, 127.61, 127.55, 127.1, 126.1, 125.9, 119.0, 105.5, 73.3, 70.6, 68.8, 65.5, 62.2, 55.2, 45.3, 18.3. Mass spectrum (API-TIS) m/z 412 (M+NH4)+.

Source