تفاعل #502113

معادلة التفاعل

1,1,1-tris(hydroxymethyl)ethane

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

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

triethylamine

→

title compound

المردود 66.0%

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

المردود 66.0%

المذيبات

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   ترشيحfiltered
2. 2
   تركيزthe filtrate was concentrated to dryness
3. 3
   workup.ADDITIONThe residue was diluted with EtOAc
4. 4
   غسيلwashed with 1N HCl (2×), saturated NaHCO3, and brine
5. 5
   تجفيفdried over Na2SO4
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated
8. 8
   أخرىThe resulting material was purified by crystallization (2×) from EtOAc/Hexanes (1:3 v:v)

الإجراء التجريبي

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)+).

المصدر