CN107473941B - 一种环丙基取代的烯丙醇及其不对称合成方法 - Google Patents
一种环丙基取代的烯丙醇及其不对称合成方法 Download PDFInfo
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Abstract
本发明涉及一种环丙基取代的烯丙醇及其不对称合成方法。该方法以单磺酰手性二胺与金属钌、铑、铱的配合物为催化剂,通过不对称转移氢化反应制备光学活性环丙基取代的烯丙醇。该方法反应条件温和,操作简便,原料易得、底物适用范围广、对映选择性高,在合成银屑病治疗药物卡泊三醇方面具有重要的应用前景。
Description
技术领域
本发明属于不对称催化技术领域,具体涉及一种环丙基取代的烯丙醇及其不对称合成方法。
背景技术
环丙基取代的手性烯丙醇是合成许多天然产物、药物、农药、生物活性物质的中间体,如治疗牛皮癣的卡泊三醇,(Angew.Chem.Int.Ed.2013,52,1890),作为目前上市的药物,卡泊三醇在治疗牛皮癣有着良好的疗效,但由于其分子内含有环丙基,且多个手性羟基的构建导致合成该类化合物存在步骤多,效率低的一系列不足。开发操作简单、经济、反应条件温和的不对称合成新方法具有重要的价值。不对称转移氢化具有操作简单,不需要氢气和高压设备等优势,在手性醇的不对称合成中越来越受到重视。手性二胺配体比手性膦配体稳定、合成简单、价格相对便宜,在不对称转移氢化反应中受到广泛欢迎。但是到目前为止,关于环丙基取代的手性烯丙醇的不对称转移氢化合成鲜有报道。
发明内容
本发明的目的在于提供一种光学活性环丙基取代的手性烯丙醇的制备方法,本发明提供的合成方法是在一定的溶剂下,在氢源,手性催化剂的作用下,通过对α,β-不饱和环丙基酮(I) 进行不对称转移氢化反应,得到环丙基取代的手性烯丙醇(II)。
R是氢、C1-C10烷基、C1-C10烷基氧基、卤代烷基、卤素、羟基、氨基、硝基、氰基;
R是氢、C1-C3烷基、C1-C3烷基氧基、三氟甲基、氟、氯、溴、羟基、氨基、硝基、氰基;
上面给出的化合物I或II的定义中,所用术语不论单独使用还是用在复合词中,代表如下取代基:
卤素:指氟、氯、溴、碘;
烷基:指直链或支链烷基;
卤代烷基:指直链或支链烷基,在这些烷基上的氢原子部分或全部被卤原子取代;
本发明提供的不对称合成方法中所涉及的手性催化剂为单磺酰手性二胺与金属钌、铑、铱的配合物,具体为(R,R)-或(S,S)-N-单磺酰-二芳基手性乙二胺与过渡金属钌、铑或者铱的配合物,其结构通式如式III、式IV所示,
所述结构通式III和IV中,M为Ru、Rh或Ir;
Ar为苯基或对甲氧基、甲基取代的苯基、萘基;
R为-CH3、-CF3、-C6H5、4-CH3C6H4、4-CF3C6H4、4-(t-Bu)-C6H4-、3,4-(CH3)2-C6H3-、 2,4,6-(CH3)3-C6H2-、2,6-Cl2-C6H3-、2,4,6-(i-Pr)3-C6H2-、C6F5、或萘基;
R’为H、CH3、i-Pr;
L为苯、1,4-二甲基苯、1-甲基-4-异丙基苯、1,3,5-三甲基苯、1,2,3,4,5-五甲基苯、1,2,3,4,5,6- 六甲基苯或五甲基环戊二烯;
X为Cl-、[OTf]-、[PF6]-、[BF4]-、[SbF6]-或手性磷酸阴离子,Y为C、O;
本发明提供的不对称合成方法中所涉及的氢源为任意比例的三乙胺和甲酸的混合物、甲酸钠、异丙醇、氢气、汉斯酯以及上述不同氢源二种或多种任意比例的混合物;
本发明提供的不对称合成方法中所涉及的溶剂为水、甲醇、乙醇、异丙醇、二氯甲烷、氯仿、1,2-二氯乙烷、苯、甲苯、二甲苯、四氢呋喃、二氧六环,二甲基亚砜、N,N-二甲基甲酰胺,以及一种或多种上述有机溶剂任意比例的混合物;
本发明涉及一种环丙基取代的手性烯丙醇的不对称合成新方法。本发明与现有技术相比具有如下优点:所用手性二胺配体稳定、合成简单、价格相对便宜、市场上可以买到;实验操作方便、安全、反应条件温和等。利用本发明提供的方法所得到的手性产物,是重要的医药或手性配体的中间体,因而本方法具有重要的工业应用价值。
具体实施方式
下面结合具体实施例,对本发明作进一步说明,但本发明并不限于以下实施例。
本发明中所用手性催化剂通用制备方法:手性二胺配体与金属前体室温下溶解在二氯甲烷中,以三乙胺为碱,室温下反应30分钟,处理后得到固体(用该方法得到催化剂A-J);该固体与等当量的三氟甲磺酸银或者四氟硼酸银或者六氟磷酸银通过离子交换得到相应的催化剂。
本发明合成的代表性催化剂(编号为A-J,其中催化剂I和G直接购买)的结构如下所示:
具体实施方式
实施例1:催化剂A-J,对(E)-苯乙烯基环丙甲醇不对称合成
将0.01mmol编号为A-J的催化剂分别加到10毫升的Schlenk试管中,加入0.2mmol(E) -苯乙烯基环丙甲酮,分别加入氢源,不同溶剂,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并有机相浓缩至干,使用催化剂E,甲酸:三乙胺(5:2,V/V)时产率和对映体过量值最高,分离产率90%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-苯乙烯基环丙甲醇的对映体过量81%的ee值,结果如表1所示。HPLC分离条件:手性柱大赛璐OD-H柱,流动相:正己烷/异丙醇= 90:10(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温:30摄氏度,t1=9.42分钟,t2=14.96分钟;1H NMR(400MHz,CDCl3):δ=7.59(t,J=1.6Hz,1H),7.57(t,J=1.6Hz,1H), 7.32-7.28(m,1H),7.15(dd,J1=1.6Hz,J2=1.6Hz,1H),7.00(dd,J1=16.0Hz,J2=16.0Hz,1H), 6.28(dd,J1=16.0Hz,J2=16.0Hz,1H),3.75-3.71(m,1H),1,98(s,1H),0.67-0.61(m,2H), 0.49-0.46(m,1H),0.41-0.37(m,1H),ppm;13C NMR(100 MHz,CDCl3):δ=136.72,134.00, 132.93,128.90,128.88,127.49,127.13,127.76,76.92,17.60,3.33,2.26,ppm.
表 1
实施例2:(S,E)-(4-甲基苯乙烯基)环丙甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E)-(4-甲基苯乙烯基)环丙甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并浓缩至干,分离产率:93%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(4-甲基苯乙烯基)环丙甲醇的对映体过量73%的ee值。HPLC分离条件:手性柱大赛璐OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温:30摄氏度,t1 =12.28分钟,t2=14.00分钟;1H NMR(400MHz,CDCl3):δ=7.33(t,J=7.2Hz,2H),7.16(t,J =6.8Hz,2H),6.63-6.55(m,1H),6.33-6.25(m,1H),3.67(t,J=6.8Hz,1H),2.37(d,J=6.8Hz, 2H),2.38(s,1H),1.14-1.10(m,1H),0.64-0.57(m,2H),0.46-0.43(m,1H),0.37-0.33(m,1H),ppm;13C NMR(100MHz,CDCl3):δ=137.44,134.00,130.01,129.92,129.27,126.42,77.11,21.20,17.68,3.18,2.20,ppm.
实施例3:(S,E)-4-三氟甲基苯乙烯基)环丙甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol0.2mmol (E)-(4-三氟甲基苯乙烯基)环丙甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并浓缩至干,分离产率:95%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(4-三氟甲基苯乙烯基)环丙甲醇的对映体过量82%的ee值。HPLC分离条件:手性柱大赛璐OD-H 柱,流动相:正己烷/异丙醇=99:1(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温: 30摄氏度,t1=30.51分钟,t2=32.84分钟;1H NMR(400MHz,CDCl3):δ=7.60(d,J=8.4Hz, 2H),7.52(d,J=8.0Hz,2H),6.69(dd,J=16.0Hz,1H),6.46(dd,J=16.0Hz,1H),3.69(dd,J1= 5.6Hz,J2=6.4Hz,1H),1.99(s,1H),1.15-1.09(m,1H),0.67-0.62(m,2H),0.50-0.40(m,1H), 0.39-0.36(m,1H),ppm;13C NMR(100MHz,CDCl3):δ=140.37,133.67,129.51,129.19,128.45,126.64125.53(dd,J=39Hz,1C),125.55,76.79,17.70,3.29,2.33,ppm.
实施例4:(S,E)-(萘乙烯基)环丙甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E) -(萘乙烯基)环丙甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并浓缩至干,分离产率:96%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(萘乙烯基)环丙甲醇的对映体过量83%的ee值。HPLC分离条件:手性柱大赛璐OD-H柱,流动相:正己烷/异丙醇=80:20(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温:30摄氏度,t1=9.37分钟, t2=13.36分钟;1H NMR(400MHz,CDCl3):δ=8.13(dd,J1=1.6Hz,J2=2.0Hz,1H),7.85(dd, J1=2.4Hz,J2=2.0Hz,1H),7.78(d,J=8.0Hz,1H),7.62(t,J=6.8Hz,1H),7.52-7.43(m,3H), 7.37(d,J=16.0Hz,1H),6.35(dd,J=16.0Hz,1H),3.79(t,J=7.2Hz,1H),1.87(s,1H), 1.21-1.12(m,1H),0.65-0.61(m,2H),0.51-0.43(m,1H),0.42-0.37(m,1H),ppm;13C NMR(100 MHz,CDCl3):δ=134.61,134.20,133.62,131.22,128.55,127.97,127.20,126.04,125.79,125.63, 123.90,123.81,77.20,17.82,3.32,2.28,ppm.
实施例5:(S,E)-(二茂铁乙烯基)环丙甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E) -(二茂铁乙烯基)环丙甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并有机相浓缩至干,分离产率80%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(二茂铁乙烯基)环丙甲醇的对映体过量50%的ee值。HPLC分离条件:手性柱大赛璐OD-H柱,流动相:正己烷/异丙醇=90:20(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温:30摄氏度,t1=14.23分钟,t2=19.66分钟;1H NMR(400MHz,CDCl3):δ=6.36(dd,J=16.0Hz, 1H),5.93(dd,J=16.0Hz,1H),4.39-4.36(m,2H),4.25(t,J=1.6Hz,2H),4.15(t,J=1.6Hz,2H), 3.60-3.56(m,1H),2.08(s,1H),1.13-1.04(m,1H),0.67-0.56(m,2H),0.46-0.41(m,1H),0.36-0.31 (m,1H),ppm;13CNMR(100MHz,CDCl3):δ=128.12,127.93,82.61,77.32,69.23,68.75,68.73, 67.03,66.75,17.62,3.30,2.15,ppm.
实施例6:(S,E)-(2-氯苯乙烯基)环丙甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E) -(2-氯苯乙烯基)环丙甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并有机相浓缩至干,分离产率:94%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(2-氯苯乙烯基)环丙甲醇的对映体过量85%的ee值。HPLC分离条件:手性柱大赛璐OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温:30摄氏度,t1=17.373分钟,t2=35.54分钟;1H NMR(400MHz,CDCl3):δ=7.59-7.56(m,2H), 7.32-7.28(m,1H),7.16-7.11(m,1H),6.96(dd,J1=1.2Hz,J2=16.0Hz,1H),6.28(dd,J1=6.4 Hz,J2=16.0Hz,1H),3.75-3.71(m,1H),1.98(s,1H),1.17-1.11(m,1H),0.67-0.59(m,2H), 0.51-0.45(m,1H),0.41-0.36(m,1H),ppm;13C NMR(100MHz,CDCl3):δ=136.71,134.00, 132.93,128.90,128.88,127.49,127.13,123.76,76.92,17.60,3.33,2.26,ppm.
实施例7:(S,E)-(4-叔丁基苯乙烯基)环丙基甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E)-(4-叔丁基苯乙烯基)环丙基甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换 3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并有机相浓缩至干,分离产率:96%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(4-叔丁基苯乙烯基)环丙基甲醇的对映体过量95%的ee值。HPLC分离条件:手性柱大赛璐OD-H 柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温: 30摄氏度,t1=8.67分钟,t2=11.06分钟;1H NMR(400MHz,CDCl3):δ=7.39(s,4H),6.62(dd, J1=1.2Hz,J2=16.0Hz,1H),3.72-3.68(m,1H),1.88(s,1H),1.36(s,9H),1.17-1.09(m,1H), 0.65-0.58(m,2H),0.47-0.44(m,1H),0.39-0.34(m,1H),ppm;13C NMR(100MHz,CDCl3):δ=150.76,134.03,130.20,129.87,126.25,125.51,77.13,34.60,31.32,17.71,3.22,2.17,ppm.
实施例8:(S,E)-(3-甲氧基苯乙烯基)环丙基甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E)-(3-甲氧基苯乙烯基)环丙基甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换 3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并有机相浓缩至干,分离产率:97%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(3-甲氧基苯乙烯基)环丙基甲醇的对映体过量81%的ee值。HPLC分离条件:手性柱大赛璐AD-H 柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温:30摄氏度,t1=14.06分钟,t2=16.08分钟;1H NMR(400MHz,CDCl3):δ=7.54-7.38(m, 6H),7.27-7.23(m,1H),7.05-6.96(m,3H),6.39(dd,J1=6.4Hz,J2=16.0Hz,1H),5.15(s,2H), 3.73-3.69(m,1H),1.90(s,1H),1.18-1.09(m,1H),0.67-0.55(m,2H),0.49-0.43(m,1H),0.39-0.33 (m,1H);13C NMR(100MHz,CDCl3):δ=137.16,131.76,128.67,128.59,127.91,127.30,127.07,126.24,125.11,121.06,112.59,77.44,70.73,17.61,3.24,2.16.
实施例9:(S,E)-(2-氯-5-硝基苯乙烯基)环丙基甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E) -(2,氯-5-硝基苯乙烯基)环丙基甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并有机相浓缩至干,分离产率:88%(石油醚:乙酸乙酯=3:1),HPLC测定产物(E)-(2,氯-5-硝基苯乙烯基)环丙基甲醇的对映体过量87%的ee值。HPLC分离条件:手性柱大赛璐OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0毫升/分钟,波长:254纳米,柱温:30摄氏度,t1=14.04分钟,t2=19.23分钟;1H NMR(400MHz,CDCl3):δ=8.46(d, J=2.8Hz,1H),8.06(dd,J1=2.8Hz,J2=2.8Hz,1H),7.56(t,J=6.8Hz,1H),7.05(dd,J=16.0 Hz,1H),6.54(dd,J=16.0Hz,1H),3.74(dd,J1=1.6Hz,J2=4Hz,1H),1.91(s,1H),1.17-1.12 (m,1H),0.71-0.67(m,2H),0.52-0.48(m,1H),0.44-0.40(m,1H),ppm;13C NMR(100MHz, CDCl3):δ=139.59,137.09,136.69,130.66,124.08,122.79,121.81,76.59,17.71,3.41,2.41,ppm.
实施例10:(S,E)-(1-苯基4,5-乙烯基丁烷)环丙基甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E) -(1-苯基4,5-乙烯基丁烷)环丙基甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并有机相浓缩至干,分离产率50%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(1- 苯基4,5-乙烯基丁烷)环丙基甲醇的对映体过量81%的ee值。HPLC分离条件:手性柱大赛璐OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0毫升/分钟,波长:210 纳米,柱温:30摄氏度,t1=15.09分钟,t2=17.53分钟;1H NMR(400MHz,CDCl3):δ= 7.35-7.31(m,2H),7.25-7.22(m,3H),5.79-5.59(m,2H),3.48(t,J=7.2Hz,1H),2.76(t,J=7.2 Hz,2H),2.45-2.39(m,2H),1.77(s,1H),1.04-0.99(m,1H),0.59-0.51(m,2H),0.39-0.34(m,1H), 0.30-0.24(m,1H),ppm;13C NMR(100MHz,CDCl3):δ=141.78,132.09,130.87,128.49,128.32, 125.86,76.99,35.66,34.07,55.49,17.56,3.13,2.07,ppm.
实施例11:(S,E)-(3,4-二甲氧基苯乙烯基)环丙基甲醇的不对称合成
将催化剂E(0.01mmol,3.26mg)加到10毫升的Schlenk试管中,加入0.2mmol(E) -(3,4-二甲氧基苯乙烯基)环丙基甲酮,甲酸:三乙胺(5:2,v/v)1mL,密封试管,用氮气置换3次气体,50℃反应24小时。反应结束后用水洗,水相用乙酸乙酯萃取3次,合并有机相浓缩至干,分离产率89%(石油醚:乙酸乙酯=3:1),HPLC测定产物(S,E)-(3, 4-二甲氧基苯乙烯基)环丙基甲醇的对映体过量71%的ee值。HPLC分离条件:手性柱大赛璐AD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0毫升/分钟,波长:254 纳米,柱温:30摄氏度,t1=25.09分钟,t2=31.53分钟;1H NMR(400MHz,CDCl3):δ= 7.00-6.96(m,2H),6.86(d,J=8.4Hz,1H),6.56(dd,J1=1.2Hz,J2=16.0Hz,1H),6.23(dd,J1= 1.6Hz,J2=16.0Hz,1H),3.95(s,3H),3.92(s,3H),3.69-3.65(m,1H),1.76(s,1H),1.16-1.10(m, 1H),0.68-0.58(m,2H),0.49-0.42(m,1H),0.39-0.34(m,1H),ppm;13C NMR(100MHz,CDCl3): δ=149.06,148.88,129.94,129.87,129.05,119.76,111.13,108.87,77.23,55.95,55.85,17.76,3.21,2.31,ppm.
Claims (3)
1.一种环丙基取代的烯丙醇的制备方法,其特征在于,在溶剂条件下,在氢源,手性催化剂的作用下,通过对环丙基取代的α,β-不饱和酮(I)进行不对称转移氢化反应,得到光学活性的环丙基取代的烯丙醇(II),反应式如下:
其中,Ar选自
中的任意一种,所述的R为氢、C1-C10烷基、C1-C10烷基氧基、卤代烷基、卤素、羟基、氨基、硝基、氰基中的任意一种;所述手性催化剂为(R,R)-或(S,S)-N-单磺酰-二芳基手性乙二胺与过渡金属钌、铑或者铱的配合物,其结构通式如式III、式IV所示,
所述结构通式III和IV中,M为Ru、Rh或Ir;Ar为苯基或对甲氧基、甲基取代的苯基、萘基;R为-CH3、-CF3、-C6H5、4-CH3C6H4、4-CF3C6H4、4-(t-Bu)-C6H4-、3,4-(CH3)2-C6H3-、2,4,6-(CH3)3-C6H2-、2,6-Cl2-C6H3-、2,4,6-(i-Pr)3-C6H2-、C6F5、或萘基;
R’为H、CH3、i-Pr;
L为苯、1,4-二甲基苯、1-甲基-4-异丙基苯、1,3,5-三甲基苯、1,2,3,4,5-五甲基苯、1,2,3,4,5,6-六甲基苯或五甲基环戊二烯;X为Cl-、[OTf]-、[PF6]-、[BF4]-、[SbF6]-或手性磷酸阴离子;
Y为CH2、O;
上面给出的化合物II的定义中,所用术语不论单独使用还是用在复合词中,代表如下取代基:卤素:指氟、氯、溴、碘;烷基:指直链或支链烷基;卤代烷基:指直链或支链烷基,在这些烷基上的氢原子部分或全部被卤原子取代。
2.根据权利要求1所述的环丙基取代的烯丙醇的制备方法,其特征在于,所用氢源为任意比例的三乙胺和甲酸的混合物、甲酸钠、异丙醇、氢气、汉斯酯以及上述不同氢源二种或多种任意比例的混合物。
3.根据权利要求1所述的环丙基取代的烯丙醇的制备方法,其特征在于,所用溶剂为水、甲醇、乙醇、异丙醇、二氯甲烷、氯仿、1,2-二氯乙烷、苯、甲苯、二甲苯、四氢呋喃、二氧六环,二甲基亚砜、N,N-二甲基甲酰胺,以及一种或多种上述有机溶剂任意比例的混合物。
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