反应 #43392

反应方程式

(2E)-1-(2,5-difluorophenyl)-3-phenylprop-2-en-1-one

N-benzylhydroxylamine hydrochloride

N-benzylhydroxylamine hydrochloride

→

2-benzyl-5-(2,5-difluorophenyl)-3-phenylisoxazolidin-5-ol

溶剂

ethanol

反应条件

后处理

1. 1
   温度was heated
2. 2
   温度the mixture was heated
3. 3
   温度at reflux for 16 h
4. 4
   其他The reaction mixture was partitioned between saturated sodium bicarbonate solution (50 mL) and ethyl acetate (2×50 mL)
5. 5
   干燥The combined organic layers were dried over sodium sulfate
6. 6
   浓缩concentrated
7. 7
   其他The residue was purified by flash column chromatography (silica, 100% hexanes initially

实验过程

A mixture of (2E)-1-(2,5-difluorophenyl)-3-phenylprop-2-en-1-one (1-1) (500 mg, 2.05 mmol, 1 equiv) and N-benzylhydroxylamine hydrochloride (327 mg, 2.05 mmol, 1.00 equiv) was heated at reflux in ethanol (10 mL) for 4 h. Additional N-benzylhydroxylamine hydrochloride (327 mg, 2.05 mmol, 1.00 equiv) was added and the mixture was heated at reflux for 16 h. The reaction mixture was partitioned between saturated sodium bicarbonate solution (50 mL) and ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (silica, 100% hexanes initially, grading to 100% EtOAc) to give 2-benzyl-5-(2,5-difluorophenyl)-3-phenylisoxazolidin-5-ol (1-2); LRMS m/z (M+H) 368.3 found, 368.1 required. Methanesulfonyl chloride (0.093 uL, 1.20 mmol, 1.11 equiv) was added to a solution of (1-2) (400 mg, 1.09 mmol, 1 equiv) and triethylamine (0.455 mL, 3.27 mmol, 3.00 equiv) in dichloromethane (30 mL) at 0° C. and the resultant mixture was warmed to 23° C. and stirred for 30 min. The reaction mixture was partitioned between saturated sodium bicarbonate solution (50 mL) and dichloromethane (2×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (silica, 100% hexanes initially, grading to 100% EtOAc) to give 2-benzyl-5-(2,5-difluorophenyl)-3-phenyl-2,3-dihydroisoxazole (1-3) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.46-7.21 (m, 11H), 7.02 (m, 2H), 5.76 (t, 1H, J=3.0 Hz), 5.12 (d, 11H, J=2.8 Hz), 4.41 (d, 1H, J=12.8 Hz), 4.10 (d, 1H, J=12.8 Hz). LRMS m/z (M+H) 350.3 found, 350.1 required.

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