Réaction #502121

Équation de réaction

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

((4S)-2,2,4-trimethyl-1,3-dioxolan-4-yl)methan-l-ol

→

title compound

Rendement 96.5%

((4R)-2,2,4-Trimethyl-1,3-dioxolan-4-yl)methyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Rendement 96.5%

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   Autrequenched with water
2. 2
   LavageThe organic layer was washed with brine
3. 3
   Séchagedried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Autresolvent was evaporated under reduced pressure
6. 6
   AutreThe product was purified by column chromatography over silica gel eluting with 20% ethyl acetate in hexane

Mode opératoire

To a solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 32.2 g, 0.14 mol) and ((4S)-2,2,4-trimethyl-1,3-dioxolan-4-yl)methan-l-ol (15 g, 0.113 mol) in anhydrous dichloromethane (750 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbamide hydrochloride (EDAC) (23 g, 0.12 mol) and N,N-dimethylaminopyridine (DMAP, 7.5 g, 61 mmol) at room temperature under nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then quenched with water. The organic layer was washed with brine, dried over sodium sulfate, filtered, and solvent was evaporated under reduced pressure. The product was purified by column chromatography over silica gel eluting with 20% ethyl acetate in hexane to give the title compound (37.5 g, 96.5% yield) as a white solid, mp 65-66° C. 1H NMR (CDCl3) δ7.75 (d, J=8.7 Hz, 1H), 7.73 (d, J=1.2 Hz, 1H), 7.46 (dd, J=8.4 and 1.7 Hz, 1H), 7.15 (m, 2H), 4.27 (m, 1H), 4.19 (m, 2H), 4.03-3.92 (m, 2H), 3.96 (s, H), 3.69 (dd, J=8.4 and 6.0 Hz, 1H), 1.64 (d, J=7.1 Hz, 3H), 1.40 (s, 3H), 1.37 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 174.4, 157.6, 135.3, 133.7, 129.2, 128.8, 127.1, 126.1, 125.9, 119.0, 109.7, 105.5, 73.4, 66.2, 64.8, 55.2, 45.2, 26.5, 25.3, 18.4; LRMS (APIMS) m/z 362 (M+NH4)+.

Source