Реакция #502128

Уравнение реакции

(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

Растворители

CH2Cl2

Условия реакции

Обработка

1. 1
   ДругоеThe byproduct, dicyclohexyl urea, was removed by filtration
2. 2
   ДругоеThe reaction mixture was partitioned between HCl (3N, 50 mL) and CH2Cl2 (50 mL×2)
3. 3
   ПромывкаThe combined organic extracts were back washed with water, brine
4. 4
   Сушкаdried over Na2SO4
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   Другоеdried under vacuum
8. 8
   ДругоеThe product was separated by silica gel column chromatography
9. 9
   Промывкаeluting with EtOAc:hexane (1:2, Rf=0.23)
10. 10
    Другоеto give

Методика

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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