تفاعل #502128

معادلة التفاعل

(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

المذيبات

CH2Cl2

ظروف التفاعل

المعالجة

1. 1
   أخرىThe byproduct, dicyclohexyl urea, was removed by filtration
2. 2
   أخرىThe reaction mixture was partitioned between HCl (3N, 50 mL) and CH2Cl2 (50 mL×2)
3. 3
   غسيلThe combined organic extracts were back washed with water, brine
4. 4
   تجفيفdried over Na2SO4
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated
7. 7
   أخرىdried under vacuum
8. 8
   أخرىThe product was separated by silica gel column chromatography
9. 9
   غسيلeluting with EtOAc:hexane (1:2, Rf=0.23)
10. 10
    أخرىto give

الإجراء التجريبي

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)+.

المصدر