反応 #85389

反応方程式

potassium bicarbonate

(E)-2-(2-(Pyridin-3-yl)hydrazono)acetic acid hydrochloride

N-chlorosuccinimide

sodium carbonate

Methyl acrylate

→

desired product

収率 65.7%

Methyl 3-chloro-1-(pyridin-3-yl)-4,5-dihydro-1H-pyrazole-5-carboxylate

収率 65.7%

溶媒

Water

ethyl acetate

Water

反応条件

後処理

1. 1
   workup.STIRRINGthe mixture stirred at 18° C
2. 2
   workup.WAITThe reaction temperature rose from 18 to 21° C. over 1 hour
3. 3
   workup.STIRRINGthe reaction was stirred for 20 hours
4. 4
   ろ過The mixture was filtered through Celite®
5. 5
   抽出the filtrate was extracted with ethyl acetate (2×500 mL)
6. 6
   その他The organic layers were dried
7. 7
   濃縮concentrated
8. 8
   その他The residue was purified by flash column chromatography

実験手順

(E)-2-(2-(Pyridin-3-yl)hydrazono)acetic acid hydrochloride (13.6 g, 64.1 mmol) was stirred in ethyl acetate (250 mL). N-chlorosuccinimide (17.9 g, 131 mmol) was added and the reaction stirred for 10 minutes. Methyl acrylate (35.2 mL, 385 mmol) was added followed by addition of potassium bicarbonate (19.4 g, 192 mmol). Water (0.05 mL) was added and the mixture stirred at 18° C. The reaction temperature rose from 18 to 21° C. over 1 hour and the reaction was stirred for 20 hours. Water (300 mL) and saturated aqueous sodium carbonate (˜100 mL) were added. The mixture was filtered through Celite® and the filtrate was extracted with ethyl acetate (2×500 mL). The organic layers were dried and concentrated. The residue was purified by flash column chromatography using 50-100% ethyl acetate/hexanes as eluent to afford the desired product as an orange oil (10.1 g, 62.5%): 1H NMR (400 MHz, CDCl3) δ 8.30 (dd, J=2.9, 0.7 Hz, 1H), 8.18 (dd, J=4.7, 1.4 Hz, 1H), 7.38 (ddd, J=8.4, 2.9, 1.4 Hz, 1H), 7.19 (ddd, J=8.5, 4.7, 0.7 Hz, 1H), 4.81 (dd, J=12.4, 6.9 Hz, 1H), 3.79 (s, 3H), 3.56 (dd, J=17.8, 12.4 Hz, 1H), 3.34 (dd, J=17.8, 6.9 Hz, 1H); ESIMS m/z 240 ([M+H]+).

出典