反応 #502113

反応方程式

1,1,1-tris(hydroxymethyl)ethane

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

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

triethylamine

→

title compound

収率 66.0%

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

収率 66.0%

溶媒

acetonitrile

反応条件

後処理

1. 1
   ろ過filtered
2. 2
   濃縮the filtrate was concentrated to dryness
3. 3
   workup.ADDITIONThe residue was diluted with EtOAc
4. 4
   洗浄washed with 1N HCl (2×), saturated NaHCO3, and brine
5. 5
   乾燥dried over Na2SO4
6. 6
   ろ過filtered
7. 7
   濃縮concentrated
8. 8
   その他The resulting material was purified by crystallization (2×) from EtOAc/Hexanes (1:3 v:v)

実験手順

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)+).

出典