Réaction #502113

Équation de réaction

1,1,1-tris(hydroxymethyl)ethane

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

1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride

triethylamine

→

title compound

Rendement 66.0%

3-Hydroxy-2-(hydroxymethyl)-2-methylpropyl(2S)-2-(6-methoxy(2-naphthyl))-propanoate

Rendement 66.0%

Solvants

acetonitrile

Conditions de réaction

Traitement

1. 1
   Filtrationfiltered
2. 2
   Concentrationthe filtrate was concentrated to dryness
3. 3
   workup.ADDITIONThe residue was diluted with EtOAc
4. 4
   Lavagewashed with 1N HCl (2×), saturated NaHCO3, and brine
5. 5
   Séchagedried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   AutreThe resulting material was purified by crystallization (2×) from EtOAc/Hexanes (1:3 v:v)

Mode opératoire

To a stirred solution of 1,1,1-tris(hydroxymethyl)ethane (13.1 g, 109 mmol), (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 5.00 g, 21.7 mmol), 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (4.80 g, 25 mmol), and N,N-dimethylaminopyridine (DMAP, 20 mg, catalytic amount) in acetonitrile (200 mL) was added triethylamine (4.2 mL, 30 mmol). The reaction mixture was stirred at ambient temperature for 25 hours, filtered, and the filtrate was concentrated to dryness. The residue was diluted with EtOAc, washed with 1N HCl (2×), saturated NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated. The resulting material was purified by crystallization (2×) from EtOAc/Hexanes (1:3 v:v) to give the title compound (4.72 g, 66% yield) as white flakes. Mp 105° C. 1H NMR (300 MHz, CDCl3) δ 7.72 (d, J=2.0 Hz, 1H), 7.69 (d, J=2.5 Hz, 1H), 7.66 (s, 1H), 7.39 (dd, J=8.5, 1.7 Hz, 1H), 7.17-7.10 (m, 2H), 4.25 (d, J=11.3 Hz, 1H), 4.09 (d, J=11.3 Hz, 1H), 3.90 (s, 3H), 3.88 (q, J=7.1 Hz, 1H), 3.46-3.25 (m, 4H), 2.65-2.55 (m, 2H), 1.60 (d, J=7.1 Hz, 3H), 0.67 (s, 3H). 13C NMR (75 MHz, CDCl3) δ175.8, 157.7, 135.3, 133.8, 129.2, 128.9, 127.3, 126.0, 119.2, 105.6, 67.7. 67.5, 66.8, 55.3, 45.6, 40.9, 18.1, 16.7. LRMS (API-TIS) m/z 350.2 ((M+NH4)+).

Source