반응 #436442

반응 방정식

2-(2-nitroethoxy)tetrahydropyran

(2-chloro-phenyl)-propynoic acid ethyl ester

1,4-phenylene diisocyanate

triethylamine

→

title compound

수율 94.2%

5-(2-chloro-phenyl)-3-(tetrahydro-pyran-2-yloxymethyl)-isoxazole-4-carboxylic acid ethyl ester

수율 94.2%

용매

toluene

toluene

반응 조건

후처리

1. 1
   온도at reflux for 10 h
2. 2
   여과filter the reaction mixture through Celite®
3. 3
   세척washing the solids with EtOAc
4. 4
   세척Wash the filtrate with 1N HCl (500 mL) and brine (500 mL)
5. 5
   건조Dry the organics over Na2SO4
6. 6
   여과filter
7. 7
   농축concentrate under reduced pressure
8. 8
   기타Purification by flash chromatography (silica gel, 85:15 Hexanes/EtOAc)

실험 절차

Add 2-(2-nitroethoxy)tetrahydropyran (41 mL, 270 mmol) dropwise in toluene (100 mL) to a solution of (2-chloro-phenyl)-propynoic acid ethyl ester (28.3 g, 135 mmol), 1,4-phenylene diisocyanate (67 g, 420 mmol) and triethylamine (15 mL) in toluene (900 mL). Stir at reflux for 10 h. While still warm (˜70° C.), filter the reaction mixture through Celite®, washing the solids with EtOAc. Wash the filtrate with 1N HCl (500 mL) and brine (500 mL). Dry the organics over Na2SO4, filter and concentrate under reduced pressure. Purification by flash chromatography (silica gel, 85:15 Hexanes/EtOAc) gives the title compound (46.5 g, 94%). MS (m/e): 282 (M−C5H8O+H+); 1H NMR (300 MHz, CDCl3) δ 7.35–7.55 (m, 4H), 5.09 (d, J=13 Hz, 1), 4.85–4.91 (m, 2H), 4.15–4.22 (m, 2H), 3.91–4.01 (m, 1H), 3.52–3.61 (m, 1H), 1.49–1.92 (m, 6H), 1.12 (t, J=7 Hz, 3H); TLC Rf=0.53 (7:3 Hexanes/EtOAc).

출처