Réaction #502127

Équation de réaction

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

tert-butyl N-(2-hydroxyethyl)carbamate

1,3-dicyclohexylcarbodiimide

→

title compound

Rendement 82.4%

2-((tert-Butoxy)carbonylamino)ethyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Rendement 82.4%

Solvants

CH2Cl2

Conditions de réaction

Traitement

1. 1
   AutreThe byproduct, dicyclohexyl urea, was removed by filtration
2. 2
   ConcentrationThe filtrate was concentrated
3. 3
   workup.DISSOLUTIONdissolved in EtOAc (50 mL)
4. 4
   Températurecooled in a dry-ice bath
5. 5
   Autreto precipitate the remaining dicyclohexyl urea
6. 6
   Filtrationfiltered
7. 7
   ConcentrationThe filtrate was concentrated
8. 8
   workup.DISSOLUTIONdissolved in CH2Cl2 (15 mL)
9. 9
   Autreprecipitated
10. 10
    AutreThe solid was dried under vacuum

Mode opératoire

A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 7.60 g, 33.0 mmol), tert-butyl N-(2-hydroxyethyl)carbamate (5.30 g, 32.9 mmol), N,N-dimethylaminopyridine (DMAP, 0.35 g, 2.86 mmol) and 1,3-dicyclohexylcarbodiimide (6.80 g, 33.0 mmol) in CH2Cl2 (200 mL) was stirred at ambient temperature overnight. The byproduct, dicyclohexyl urea, was removed by filtration. The filtrate was concentrated, dissolved in EtOAc (50 mL) and then cooled in a dry-ice bath to precipitate the remaining dicyclohexyl urea and then filtered. The filtrate was concentrated, dissolved in CH2Cl2 (15 mL) and hexane (200 mL) and then stirred until the product precipitated. The solid was dried under vacuum to give the title compound (10.12 g, 82% yield). Mp 82-84° C. 1H NMR (300 MHz, CDCl3) δ 7.72-7.65 (m, 3H), 7.42-7.38 (m, 1H), 7.16-7.11 (m, 2H), 5.05 (br, 1H), 4.13 (t, J=5.3 Hz, 2H), 3.91 (s, 3H), 3.87 (q, J=7.1 Hz, 1H), 3.30 (br. q, 2H), 1.58 (d, J=7.1 Hz, 3H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3) δ 174.4, 157.6, 155.6, 135.4, 133.6, 129.2, 128.8, 127.1, 126.0, 125.8, 119.0, 105.5, 79.3, 63.7, 55.2, 45.2, 39.5, 28.2, 18.3. Mass spectrum (API-TIS) m/z 374 (MH)+. Anal. calcd. for C21H27NO5: C, 67.54; H, 7.29; N, 3.75. Found: C, 67.43; H, 7.16; N, 3.66.

Source