CN108659028B - 一种(z)式氟烷基化烯基硼酸酯及其制备方法和应用 - Google Patents
一种(z)式氟烷基化烯基硼酸酯及其制备方法和应用 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
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- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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Abstract
本发明公开了一种(Z)式氟烷基化烯基硼酸酯及其制备方法和应用,制备方法包括:将式Ⅱ结构的式Ⅱ结构的不对称炔烃、式Ⅲ结构的溴代氟烷基化合物、联硼酸频哪醇酯、钯催化剂、添加剂、碱及溶剂加入混合,反应完成后经后处理得到式Ⅰ结构的(Z)式氟烷基化烯基硼酸酯。本发明首次通过三组分反应实现了非对称炔烃的反式氟烷基化硼化反应,简单高效的制备了(Z)式氟烷基化烯基硼酸酯,反应条件温和,底物适用性广,并且产物进一步偶联可形成多样的三取代氟烷基化合物。
Description
技术领域
本发明涉及有机合成技术领域,具体涉及一种(Z)式氟烷基化烯基硼酸酯及其制备方法和应用。
背景技术
烯基硼酸酯类化合物是一类重要的有机合成中间体,不仅具有相对较好的稳定性,同时具有良好的反应活性,可实现多种类型的化学转变,通过卤代反应、偶联反应、共轭加成、氧化还原反应等形成新的碳碳键及碳杂原子键(炔烃的硼化反应如式1所示),被广泛用于各种医药化工中间体、天然产物和新材料合成中。因此,发展简单、高效的烯基硼酸酯类化合物显得极其重要。
一直以来含氟有机化学都是化学家们关注的热点领域之一。由于氟原子的特殊性质,在有机分子中引入含氟片段往往能够显著地改变其母体的体积、酸性、亲脂性、极性、偶极距以及化学和生物代谢稳定性,因此含氟的有机化合物已广泛地应用到医药、农药和材料等领域。二氟亚甲基(CF2) 化合物不仅有着一般含氟化合物的特性,还具有自己独特的化学性质和药用价值。二氟亚甲基常常被用于药物以及生物活性分子的设计中,二氟亚甲基(CF2)具有很好的代谢稳定性,常常被视作氧原子、羰基和亚甲基的生物电子等排体(bioisostere),同时,在官能化的二氟甲基化中,二氟亚甲基的吸电子效应还会影响到相邻官能团R的电子性质、化学性质以及反应活性。考虑到烯基化合物的多功能性,将二氟亚甲基选择性地引入烯烃分子中能显著地改变原烯烃分子的生理活性,这一策略被应用于含烯烃的药物设计中。
炔烃的碳硼化反应是最直接有效的合成多取代烯基硼酸酯的方法之一。这类化合物可以立体和区域选择性的合成三取代或是四取代的烯烃化合物。然而,通过传统的方法很难得到结构单一的烯基硼酸酯,因此,化学家们在这方面做了很多努力,直接碳硼化是有效的方法之一(直接碳硼化反应如式 2所示),同样,通过炔烃的硼金属化后碳偶联也是构建三取代烯基硼酸酯常见方法(硼金属化/碳偶联策略如式3所示)。
然而,这类反应非对称内炔烃底物却很难进行,主要是由于内炔烃的活性比末端炔烃小,加上硼金属化的区域选择性不易控制。值得注意的是,以往的报道主要局限于炔烃的顺式碳硼化,而炔烃的金属催化三组分反式-碳硼化尚未实现。本发明实现了非对称炔烃、溴代氟烷基化合物、联硼酸频哪醇酯的三组分反应,得到了(Z)式二氟亚甲基烯基硼酸酯(如式4所示),同时该硼烷烯烃的制备为合成更多多样性的四取代二氟亚甲基烯烃提供了一条有效途径。
发明内容
本发明提供了一种(Z)式氟烷基化烯基硼酸酯及其制备方法和应用,首先实现了钯催化非对称炔烃、溴代氟烷基化合物、联硼酸频哪醇酯的三组分反应,应用串联反应思路,通过自由基引发内炔二氟烷基化碳硼化,从而实现内炔烃的反式碳硼化,得到了(Z)式二氟亚甲基烯基硼酸酯(具体制备如式5所示),同时该硼烷烯烃的制备为合成更多多样性的四取代二氟亚甲基烯烃提供了一条有效途径。
一种(Z)式氟烷基化烯基硼酸酯,为式Ⅰ结构:
其中,R1为苯基、对甲基苯基、对氯苯基、对溴苯基、对氟苯基、对甲氧基苯基中的一种,R2为甲基、乙基、异丙基中的一种,Rf为二氟乙酸乙酯、二氟乙酰基苯胺、九氟丁烷、十三氟己烷中的一种。
一种(Z)式氟烷基化烯基硼酸酯的制备方法,包括如下步骤:
将式Ⅱ结构的不对称炔烃、式Ⅲ结构的溴代氟烷基化合物、联硼酸频哪醇酯(B2Pin2)、钯催化剂、添加剂、碱及溶剂加入混合,形成反应体系,反应完成后经后处理得到式Ⅰ结构的(Z)式氟烷基化烯基硼酸酯;
其中,式Ⅱ中,R1为苯基、对甲基苯基、对氯苯基、对溴苯基、对氟苯基、对甲氧基苯基中的一种,R2为甲基、乙基、异丙基中的一种;式Ⅲ中, Rf为二氟乙酸乙酯、二氟乙酰基苯胺、二氟乙酰基环己胺、二氟乙酰基苯胺中的一种;式Ⅰ中R1、R2与式Ⅱ中R1、R2具有相同含义;式Ⅰ中Rf与式Ⅲ中Rf具有相同含义
涉及的反应的具体合成路线如下所示:
通过钯催化剂实现式Ⅱ结构的不对称炔烃、式Ⅲ结构的溴代氟烷基化合物、联硼酸频哪醇酯的三组分反应。该制备方法简单、有效地实现了式Ⅰ结构的(Z)式氟烷基化烯基硼酸酯。
所述的反应体系的反应条件为:氮气氛围中,反应温度为10~40℃,反应时间为2h~12h。进一步优选,所述的反应体系的反应条件为:氮气氛围中,反应温度为75~90℃,反应时间为9h~11h。
所述的钯催化剂为四三苯基膦钯,所述的碱为碳酸铯,所述的添加剂为碘化锂所述的有机溶剂为1,2-二氯乙烷。
所述的式Ⅱ结构的不对称炔烃、式Ⅲ结构的溴代氟烷基化合物、联硼酸频哪醇酯、钯催化剂、添加剂及碱的摩尔比为1:1~3:1~2.5:0.1~0.5:1~3: 1~3。进一步优选,所述的式Ⅱ结构的不对称炔烃、式Ⅲ结构的溴代氟烷基化合物、联硼酸频哪醇酯、钯催化剂、添加剂及碱的摩尔比为1:1.5:2: 0.15:1.5:2。
所述的后处理包括:采用加水淬灭、萃取、有机相经洗涤、干燥和柱层析分离。
所述的萃取可采用乙酸乙酯作为萃取剂。
所述的洗涤可采用饱和食盐水洗。
所述的干燥可采用无水Na2SO4干燥
所述的柱层析分离的条件为:中性氧化铝,洗脱液:乙酸乙酯/石油醚的体积比=1:10。
将合成的(Z)式二氟烷基化合物用于各类偶联反应,方便制备多样的三取代二氟烷基烯烃的制备,所述的三取代二氟烷基烯烃为4a、5a或6a所示的结构:
具体的反应路线如下:
同现有技术相比,本发明具有如下优点:
1、一步实现(Z)式氟烷基化烯基硼酸酯的合成,合成效率显著提高,原子和步骤经济性高。2、首次实现了分分子间非对称炔烃的反式氟烷基硼化反应。3、合成的(Z)式氟烷基化烯基硼酸酯可多种用于三取代氟烷基化烯烃的制备。4、反应均在室温下进行,条件温和,快速高效、底物适用范围广,官能团兼容性好,具有良好应用前景;故本发明具有较大的理论创新价值以及实施价值。
具体实施方式
实施例1
取一只干净的反应管,向里面分别加入联硼酸频哪醇酯(127.0mg,0.5 mmol),四三苯基膦钯(43.3mg,0.0375mmol),碳酸铯(162.9mg,0.5mmol), 碘化锂(50.2mg,0.375mmol),抽真空换氮气三次,氮气保护下加入1,2-二氯乙烷溶液2.5mL,再依次加入1-苯丙炔2a(29.0mg,0.25mmol),1-溴- 二氟乙酸乙酯3a(76.1mg,0.375mmol)形成的反应体系,在80℃下搅拌10 小时。反应结束后向反应体系中加入4mL水淬灭反应,用乙酸乙酯萃取三次(20mL×3),合并有机相,有机相用饱和NaCl水溶液洗涤,无水Na2SO4干燥。将溶剂旋干,柱层析(EA:PE=1:10,即乙酸乙酯/石油醚的体积比= 1:10,中性氧化铝)得到黄色固体2a63.0mg,产率69%。产物波谱分析1H NMR(600MHz,CDCl3)δ7.27–7.24(m,2H),7.22–7.20(m,1H),7.09(d,J=7.2 Hz,2H),3.77(q,J=7.2Hz,2H),2.16(s,3H),1.24(s,12H),1.13(t,J=7.2Hz, 3H);13C NMR(151MHz,CDCl3)δ163.4(t,J=33.2Hz),138.2(t,J=23.3Hz),138.1(s),128.6(t,J=1.8Hz),127.6(s),126.9(s),113.0(t,J=250.34Hz),84.1 (s),62.4,24.5,17.4(t,J=4.8Hz),13.6;19F NMR(565MHz,CDCl3)δ-95.9(s, 2F);HRMS(ESI)calcd for C19H25BF2O4(M+H)+367.1887,found 367.1884。
反应式如下:
实施例2
除用结构式2b所示的不对称炔烃代替实施例1中结构式2a所示的1- 苯丙炔外,其余操作步骤同实施例1,产率:76%,黄色固体;产物波谱分析1H NMR(600MHz,CDCl3)δ7.06(d,J=7.8Hz,2H),6.98(d,J=8.0Hz, 2H),3.77(q,J=7.2Hz,2H),2.31(s,3H),2.14(s,3H),1.25(s,12H),1.13(t,J =7.2Hz,3H);13C NMR(151MHz,CDCl3)δ163.4(s),137.9(t,J=23.3Hz), 136.5(s),135.0(s),128.45(t,J=1.76Hz),128,4(s),113.0(t,J=248.8Hz), 84.1(s),62.4(s),24.5(s),21.2(s),17.4(t,J=4.8Hz),13.5(s);19F NMR(565MHz,CDCl3)δ-95.7(s);HRMS(ESI)calcd for C20H27BF2O4(M+Na)+ 403.1863,found403.1860。
反应式如下:
实施例3
除用结构式2c所示的不对称炔烃代替实施例1中结构式2a所示的1- 苯丙炔外,其余操作步骤同实施例1,产率:62%,黄色固体;产物波谱分析1H NMR(400MHz,CDCl3)δ7.23(d,J=8.4Hz,2H),7.02(d,J=8.3Hz, 2H),3.88(q,J=7.1Hz,2H),2.15(s,3H),1.24(s,12H),1.17(t,J=7.2Hz,3H);13C NMR(151MHz,CDCl3)δ163.4(t,J=33.4Hz),139.4(t,J=23.0Hz), 136.8(s),132.79(s),129.9(s),127.8(s),113.0(t,J=251.5Hz),84.2(s),62.7 (s),24.6(s),17.4(t,J=4.7Hz),13.6(s);19F NMR(565MHz,CDCl3)δ-96.4(s); HRMS(ESI)calcd for C19H24BClF2O4(M+H)+401.1497,found 401.1502。
反应式如下:
实施例4
除用结构式2d所示的不对称炔烃代替实施例1中结构式2a所示的1- 苯丙炔外,其余操作步骤同实施例1,产率:64%,黄色固体;产物波谱分析1H NMR(600MHz,CDCl3)δ7.39(d,J=8.4Hz,2H),6.97(d,J=8.3Hz, 2H),3.87(q,J=7.2Hz,2H),2.15(s,3H),1.24(s,12H),1.18(t,J=7.2Hz,3H);13C NMR(151MHz,CDCl3)δ163.4(t,J=33.5Hz),139.35(t,J=23.0Hz), 137.3(s),130.76(s),130.27(s),121.0(s),114.69(s),113.03(t,J=251.4Hz), 84.26(s),62.7(s),24.56(s),17.45(t,J=4.7Hz),13.6(s);19F NMR(565MHz,CDCl3)δ-96.4(s);HRMS(ESI)calcd for C19H24BBrF2O4(M+NH4)+462.1257, found462.1265。
反应式如下:
实施例5
除用结构式2e所示的不对称炔烃代替实施例1中结构式2a所示的1- 苯丙炔外,其余操作步骤同实施例1,产率:60%,黄色固体;产物波谱分析1H NMR(600MHz,CDCl3)δ7.06(dd,J=8.5,5.5Hz,2H),6.95(t,J=8.7 Hz,2H),3.86(q,J=7.2Hz,2H),2.15(s,3H),1.24(s,12H),1.17(t,J=7.2Hz, 3H);13C NMR(151MHz,CDCl3)δ163.4(t,J=33.4Hz),161.85(d,J=246.0 Hz),139.2(t,J=22.2Hz),134.1(d,J=3.4Hz),130.3(d,J=7.9Hz),114.6(d, J=21.4Hz),113.0(t,J=250.7Hz),84.2(s),62.6(s),24.5(s),17.4(t,J=4.8 Hz),13.6(s);19F NMR(565MHz,CDCl3)δ-96.1(s),-115.5(s);HRMS(ESI) calcd for C19H24BF3O4(M+Na)+407.1612,found 407.1613。
反应式如下:
实施例6
除用结构式2f所示的不对称炔烃代替实施例1中结构式2a所示的对甲苯磺酰基苯炔外,其余操作步骤同实施例1,产率:78%,黄色固体;产物波谱分析1H NMR(600MHz,CDCl3)δ7.02(d,J=8.7Hz,2H),6.81–6.78(m, 2H),3.81–3.77(m,5H),2.14(s,3H),1.25(s,12H),1.13(t,J=7.2Hz,3H);13C NMR(151MHz,CDCl3)δ163.5(t,J=20.1Hz),158.6(s),138.0(t,J=23.3 Hz),130.3(s),129.94(s),113.1(s),113.1(t,J=250.4Hz),84.1(s),62.4(s),55.1(s),24.6(s),17.3(t,J=4.8Hz),13.6(s);19F NMR(565MHz,CDCl3)δ -95.4(s);HRMS(ESI)calcd for C20H27BF2O5(M+H)+397.1992,found 397.1992。
反应式如下:
实施例7
除用结构式2g所示的不对称炔烃代替实施例1中结构式2a所示的1- 苯丙炔外,其余操作步骤同实施例1,产率:52%,黄色固体;产物波谱分析1H NMR(600MHz,CDCl3)δ7.27–7.25(m,2H),7.22–7.20(m,1H),7.11(d, J=7.3Hz,2H),3.73(q,J=7.1Hz,2H),2.54(q,J=7.3Hz,2H),1.25–1.23(m, 15H),1.11(t,J=7.1Hz,3H);13C NMR(151MHz,CDCl3)δ163.4(t,J=33.6 Hz),143.8(t,J=22.1Hz),137.8(s),128.7(s),127.7(s),127.0(s),113.36(t,J= 249.4Hz),84.1(s),62.4(s),25.4(t,J=3.7Hz),24.5(s),15.1(s),13.5(s);19FNMR(565MHz,CDCl3)δ-93.9(s);HRMS(ESI)calcd for C20H27BF2O4(M+ Na)+403.1863,found403.1864。
反应式如下:
实施例8
除用结构式2h所示的不对称炔烃代替实施例1中结构式2a所示的1- 苯丙炔外,其余操作步骤同实施例1,产率:40%,黄色固体;产物波谱分析1H NMR(600MHz,CDCl3)δ7.19–7.17(m,2H),7.15–7.12(m,1H),7.05(d, J=7.1Hz,2H),3.65(q,J=7.2Hz,2H),2.84–2.79(m,1H),1.27(d,J=7.2Hz, 6H),1.14(s,12H),1.04(t,J=7.2Hz,3H);13C NMR(151MHz,CDCl3)δ163.0 (t,J=29.37Hz),139.4(s),139.16(t,J=22.2Hz),128.2(s),127.5(s),126.3(s), 114.7(t,J=255.3Hz),84.0(s),41.65(s),24.5(s),22.0(s),18.5(t,J=5.1Hz);19F NMR(565MHz,CDCl3)δ-92.10(s);HRMS(ESI)calcd for C21H29BF2O4 (M+K)+433.1759,found 433.1755。
反应式如下:
实施例9
除用结构式3b所示的1-溴-二氟乙酰苄胺代替实施例1中结构式3a所示的1-溴-二氟乙酸乙酯外,其余操作步骤同实施例1,产率:73%,黄色固体;产物波谱分析1H NMR(400MHz,CDCl3)δ7.33–7.27(m,3H),7.20–7.12 (m,5H),7.08–7.04(m,2H),5.84(s,1H),4.08(d,J=5.6Hz,2H),2.22(s,3H), 1.22(s,12H);13C NMR(151MHz,CDCl3)δ163.9(t,J=29.7Hz),139.5(t,J= 22.4Hz),139.2(s),136.5(s),128.7(s),128.3(s),128.0(s),127.8(s),127.5(s), 126.4(s),114.6(t,J=255.1Hz),84.0(s),43.6(s),24.53(s),18.33(t,J=5.0 Hz);19F NMR(565MHz,CDCl3)δ-96.90(s);HRMS(ESI)calcd forC24H28BF2NO3(M+NH4)+445.2469,found 445.2469。
反应式如下:
实施例10
除用结构式3c所示的1-溴-二氟乙酰环己胺代替实施例1中结构式3a 所示的1-溴-二氟乙酸乙酯外,其余操作步骤同实施例1,产率:77%,黄色固体;产物波谱分析1H NMR(600MHz,CDCl3)δ7.26–7.22(m,2H), 7.20–7.17(m,1H),7.11–7.06(m,2H),5.58(d,J=6.3Hz,1H),3.50–3.42(m, 1H),2.19(s,3H),1.76–1.72(m,2H),1.66–1.61(m,2H),1.60–1.55(m,1H), 1.33–1.27(m,2H),1.22(s,12H),1.14–1.08(m,1H),0.97–0.95(m,2H);13CNMR(151MHz,CDCl3)δ162.9(t,J=29.4Hz),139.4(s),138.9(t,J=22.1 Hz),128.0(s),127.5(s),126.3(s),114.8(t,J=225.5Hz),83.9(s),48.3(s),32.2 (s),25.3(s),24.5(s),18.52(t,J=4.9Hz);19F NMR(565MHz,CDCl3)δ-97.31 (s);HRMS(ESI)calcd forC23H32BF2NO3(M+NH4)+437.2782,found 437.2781。
反应式如下:
实施例11
除用结构式3b所示的1-溴-二氟乙酰苯胺代替实施例1中结构式3a所示的1-溴-二氟乙酸乙酯外,其余操作步骤同实施例1,产率:60%,黄色固体;产物波谱分析1H NMR(600MHz,CDCl3)δ7.27(dd,J=8.8,5.8Hz,3H), 7.16(t,J=7.5Hz,3H),7.14–7.05(m,5H),2.26(s,3H),1.22(s,12H);13C NMR (151MHz,CDCl3)δ161.7(t,J=29.3Hz),139.6(t,J=22.3Hz),139.1(s), 136.2(s),128.8(s),128.2(s),127.6(s),126.6(s),125.0(s),119.8(s),114.6(t,J =257.4Hz),84.1(s),24.6(s),18.37(t,J=4.9Hz);19F NMR(565MHz,CDCl3) δ-96.96(s);HRMS(ESI)calcd for C23H26BF2NO3(M+NH4)+431.2312,found431.2311。
反应式如下:
实施例12
取一只干净的反应管,向里面分别加入(Z)式氟烷基化烯基硼酸酯1a (91.5mg,0.25mmol),四三苯基膦钯(8.6mg,0.0075mmol),碳酸钾(103.6 mg,0.75mmol),抽真空换氮气三次,氮气保护下加入1,2-二氯乙烷溶液2.5 mL,再依次加入溴苯(47.1mg,0.30mmol),1-溴-二氟乙酸乙酯3a(76.1mg, 0.375mmol)形成的反应体系,在120℃下搅拌12小时。反应结束后向反应体系中加入4mL水淬灭反应,用乙酸乙酯萃取三次(20mL×3),合并有机相,有机相用饱和NaCl水溶液洗涤,无水Na2SO4干燥。将溶剂旋干,柱层析(EA:PE=1:20,即乙酸乙酯/石油醚的体积比=1:20,硅胶330-370目) 得到无色液体4a 74.3mg,产率94%。产物波谱分析1H NMR(600MHz, CDCl3)δ7.31(d,J=7.7Hz,2H),7.27–7.25(m,4H),7.17–7.11(m,4H),3.79(q, J=7.2Hz,2H),1.96(s,3H),1.17(t,J=7.2Hz,3H);13C NMR(151MHz, CDCl3)δ163.65(t,J=33.6Hz),146.34(t,J=7.3Hz),141.55(s),139.76(s), 129.85(s),128.9(s),128.2(s),127.84(s),127.8(s);127.52(s),127.2(t,J=24.0 Hz),114.0(t,J=248.5Hz),62.5(s),15.97(t,J=4.6Hz),13.6(s);19F NMR (565MHz,CDCl3)δ-94.26(s);HRMS(ESI)calcd for C19H18F2O2(M+H)+ 317.1348,found 317.1348。
反应式如下:
实施例13
取一只干净的反应管,向里面分别加入(Z)式氟烷基化烯基硼酸酯1a (91.5mg,0.25mmol),四三苯基膦钯(8.6mg,0.0075mmol),碳酸铯(244.4 mg,0.75mmol),抽真空换氮气三次,β-溴苯乙烯(54.6mg,0.30mmol),1- 溴-二氟乙酸乙酯3a(76.1mg,0.375mmol)形成的反应体系,在80℃下搅拌12小时。反应结束后向反应体系中加入4mL水淬灭反应,用乙酸乙酯萃取三次(20mL×3),合并有机相,有机相用饱和NaCl水溶液洗涤,无水Na2SO4干燥。将溶剂旋干,柱层析(EA:PE=1:20,即乙酸乙酯/石油醚的体积比= 1:20,硅胶330-370目)得到无色液体5a 64.0mg,产率75%。产物波谱分析1H NMR(400MHz,CDCl3)δ7.37–7.21(m,9H),7.14–7.12(m),6.00(d,J= 15.8Hz,1H),3.88(q,J=7.1Hz,2H),2.21(s,3H),1.18(t,J=7.2Hz,3H);13C NMR(151MHz,CDCl3)δ163.7(t,J=30.7),142.3(t,J=7.7),136.8(s),136.6 (s),136.5(s),130.7(s),128.6(s),128.3(s),127.9(s),127.8(s),127.7(s),126.8 (s),113.8(t,J=248.2Hz),62.56(s),13.65(s),13.41(s);19F NMR(565MHz,CDCl3)δ-94.35(s,2F);HRMS(ESI)calcd for C21H20F2O2(M+H)+343.1504, found 343.1499。
反应式如下:
实施例14
氮气氛围下,取一只干净的反应管,向里面分别加入(Z)式氟烷基化烯基硼酸酯1a(91.5mg,0.25mmol),三(二亚苄基丙酮)二钯(11.0mg, 0.0125mmol),三(邻甲基苯基)磷(7.6mg,0.025mmol),碳酸铯(162.9mg, 0.5mmol),1.8mL的N,N-二甲基甲酰胺及0.2mL的水作混合溶剂,再加入碘甲烷(53.2mg,0.375mmol)形成的反应体系,在60℃下搅拌12小时。反应结束后向反应体系中加入4mL水淬灭反应,用乙酸乙酯萃取三次(20 mL×3),合并有机相,有机相用饱和NaCl水溶液洗涤,无水Na2SO4干燥。将溶剂旋干,柱层析(EA:PE=1:30,即乙酸乙酯/石油醚的体积比=1:30,硅胶330-370目)得到无色液体5a 64.0mg,产率80%。产物波谱分析1H NMR (600MHz,CDCl3)δ7.30–7.26(m,3H),7.11(d,J=7.5Hz,2H),3.78(q,J=7.2 Hz,2H),2.06(s,3H),1.97(s,3H),1.15(t,J=7.2Hz,3H);13C NMR(151MHz, CDCl3)δ163.9(t,J=30.0Hz),141.6(t,J=12.8Hz),128.35(t,J=1.9Hz), 127.8(s),127.4(s),113.90(t,J=247.7Hz),62.40(s),23.63(s),13.7(t,J=5.2 Hz),13.54(s);HRMS(ESI)calcd for C14H20F2NO2(M+NH4)+272.1457,found 272.1458。
反应式如下:
Claims (7)
2.根据权利要求1所述的制备方法,其特征在于,所述的反应体系的反应条件为:氮气氛围中,反应温度为75℃~90℃,反应时间为9h~11h。
3.根据权利要求1所述的制备方法,其特征在于,所述的式Ⅱ结构的不对称炔烃、式Ⅲ结构的溴代氟烷基化合物、联硼酸频哪醇酯、钯催化剂、添加剂及碱的摩尔比为1:1~3:1~2.5:0.1~0.5:1~3:1~3。
4.根据权利要求3所述的制备方法,其特征在于,所述的式Ⅱ结构的不对称炔烃、式Ⅲ结构的溴代氟烷基化合物、联硼酸频哪醇酯、钯催化剂、添加剂及碱的摩尔比为1:1.5:2:0.15:1.5:2。
5.根据权利要求1所述的制备方法,其特征在于,所述的后处理包括:采用加水淬灭、萃取、有机相经洗涤、干燥和柱层析分离。
6.根据权利要求5所述的制备方法,其特征在于,所述的萃取采用乙酸乙酯作为萃取剂;
所述的洗涤采用饱和食盐水洗;
所述的干燥采用无水Na2SO4干燥。
7.根据权利要求6所述的制备方法,其特征在于,所述的柱层析分离的条件为:中性氧化铝,洗脱液:乙酸乙酯/石油醚的体积比= 1:10。
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