反応 #502121

反応方程式

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

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

→

title compound

収率 96.5%

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

収率 96.5%

溶媒

dichloromethane

反応条件

後処理

1. 1
   その他quenched with water
2. 2
   洗浄The organic layer was washed with brine
3. 3
   乾燥dried over sodium sulfate
4. 4
   ろ過filtered
5. 5
   その他solvent was evaporated under reduced pressure
6. 6
   その他The product was purified by column chromatography over silica gel eluting with 20% ethyl acetate in hexane

実験手順

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)+.

出典