448-19-1 2-硝基-5-氟苯甲醚

中文名称: 2-硝基-5-氟苯甲醚
英文名称: 5-Fluoro-2-nitroanisole
CAS号

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名称和标识

中文名: 2-硝基-5-氟苯甲醚
英文名: 5-Fluoro-2-nitroanisole
CAS号: 448-19-1
分子式: C7H6FNO3
分子量: 171.13
中文别名: 5-氟-2-硝基苯甲醚
英文别名: 4-Fluoro-2-methoxy-1-nitrobenzene; 5-Fluoro-2-nitrophenyl methyl ether

物化属性

Ali LogS: -2.46
BBB渗透性: Yes
CYP1A2抑制剂: No
CYP2C19抑制剂: No
CYP2C9抑制剂: No
CYP2D6抑制剂

安全信息

安全说明

常温运输。危险等级为IRRITANT（刺激性），海关编码2909309090，非危险化学品。

生产及用途

用途与制备

化学合成

路线1：以4-氟-2-羟基硝基苯为原料

步骤：在5L四颈烧瓶中，加入DMF 2500g，4-氟-2-羟基硝基苯（500g，3.20mol）和碳酸钾（483g，3.50mol）并加热至60℃。滴加424g（3.36mol）硫酸二甲酯约2-3小时。滴加完成后，加热至90-100℃，保持5-6小时。取样GC分析4-氟-2-羟基硝基苯<0.5％后，将混合物冷却至50℃，产生单甲基硫酸钾盐。减压蒸馏滤液，回收DMF，得到515g 4-氟-2-甲氧基硝基苯，为黄色油状液体。
条件：碳酸钾；N,N-二甲基甲酰胺；60-100℃
收率：94.1%
GC含量：99.5%
参考文献： [1] Chemical and Pharmaceutical Bulletin, 1991, vol. 39, # 9, p. 2323 - 2332 [2] Patent: CN106083536, 2016, A. Location in patent: Paragraph 0035; 0036 [3] Heterocycles, 1992, vol. 34, # 12, p. 2301 - 2311 [4] Patent: WO2010/71885, 2010, A1. Location in patent: Page/Page column 443 [5] Patent: WO2010/115688, 2010, A1. Location in patent: Page/Page column 146

路线2：以4-硝基-2-羟基-1-硝基苯为原料

步骤：向4-硝基-2-羟基-1-硝基苯（100mg，0.637mmol）的N,N-二甲基甲酰胺（3.2mL）溶液中加入碳酸钾（132mg，0.955mmol），然后在冰冷条件下加入甲基碘（48μL，0.764mmol），室温搅拌1小时。再在冰冷条件下添加碳酸钾（132mg，0.955mmol）和甲基碘（48μL，0.764mmol），60℃搅拌1小时。反应液加水后用乙酸乙酯萃取，有机层用盐水洗涤，无水硫酸钠干燥，真空浓缩得到4-氟-2-甲氧基-1-硝基苯（118mg）。
条件：碳酸钾；N,N-二甲基甲酰胺；60℃；冰冷条件
收率：>100%
产物性质：黄色油状物；1H-NMR（CDCl3）δ：3.97（3H，s），6.74（1H，ddd，J=2.4,7.8,9.0Hz），6.80（1H，dd，J=2.4,10.2Hz），7.97（1H，dd，J=6.1,9.0Hz）

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