반응 #502128

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(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

용매

CH2Cl2

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후처리

1. 1
   기타The byproduct, dicyclohexyl urea, was removed by filtration
2. 2
   기타The reaction mixture was partitioned between HCl (3N, 50 mL) and CH2Cl2 (50 mL×2)
3. 3
   세척The combined organic extracts were back washed with water, brine
4. 4
   건조dried over Na2SO4
5. 5
   여과filtered
6. 6
   농축concentrated
7. 7
   기타dried under vacuum
8. 8
   기타The product was separated by silica gel column chromatography
9. 9
   세척eluting with EtOAc:hexane (1:2, Rf=0.23)
10. 10
    기타to give

실험 절차

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)+.

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