Ethyl (R)-4-chloro-3-hydroxybutyrate ((R)-CHBE) is a versatile fine chemistry intermediate. It is used as a precursor in the synthesis of several pharmacologically valuable products, including L-carnitine. It is usually produced by means of stereoselective biotechnology methods in enzymatic reactions. An alternative preparation strategy towards ethyl (R)-4-chloro-3-hydroxybutyrate is based on the asymmetric hydrogenation of ethyl 4-chloro-acetoacetate (ECAA) to the optically pure product ((R)-CHBE) over ((S)-Ru-BINAP) catalytic complex. The reaction conditions were optimised first using (R)-Ru-BINAP yielding the (S)-CHBE isomer. All reactions were performed under continuous regime in a microfluidic chip reactor. Three different solvent phases were employed. The methanol/water phase, the ethanol/water phase, and the [N_8,222][Tf₂N]/methanol/water phase. The attained conversions were total in all cases already at 408 K. The parameter of enantioselectivity ee was 99.4% towards the (S)-CHBE for the system in which (R)-Ru-BINAP was accommodated in [N_8,222][Tf₂N]/methanol/water phase. In the case of methanol/water experiment the ee parameter reached 92.5%. For ethanol/water ee was 91.8%. The (R)-CHBE isomer over (S)-Ru-BINAP was obtained with ee = 99.3% in the [N_8,222][Tf₂N]/methanol/water phase at 408 K. For the reactions leading to (S)-CHBE apparent activation energies were evaluated. They were similar for MeOH/water and EtOH/water (110.5 and 110.7 kJ.mol⁻¹). The apparent activation energies corresponding with the [N_8,222][Tf₂N]/MeOH/water system were much higher (of about 90 kJ.mol⁻¹) reaching the level of 200 kJ.mol⁻¹. The impact of the molecular structure of the main reactant was negligible as appeared from the comparison with hydrogenation of methylacetoacetate (MAA, ~ 200 kJ.mol⁻¹). The effect of the presence of the [N_8,222][Tf₂N] ionic liquid on the sum of the activation energy dominated. The effectiveness of the enantioselective synthesis was additionally assessed by nuclear magnetic resonance employing the method of enantioselective complexation of the chiral compound with a chiral solvating agent.

乙基（R） - 4-氯-3-羟基丁酸酯（（R） - CHBE）是一种多功能的精细化工中间体。它被用作合成多种具有药理价值的产品（包括L-肉碱）的前体。它通常是通过立体选择性生物技术方法在酶促反应中生产的。（R） -4-氯-3-羟基丁酸乙酯的另一种制备策略是基于（（S））将4-氯-乙酰乙酸乙酯（ECAA）不对称氢化为光学纯产物（（R） -CHBE ） -Ru-BINAP）催化络合物。反应条件的优化第一使用（- [R ）-的Ru-BINAP，得到的（S） -CHBE异构体。所有反应均在微流体芯片反应器中在连续条件下进行。使用了三种不同的溶剂相。甲醇/水相，乙醇/水相和[N _8,222 ] [Tf ₂ N] /甲醇/水相。在所有情况下，所获得的转化率总计已达到408K。对于其中（R） -Ru-BINAP容纳在[N _8,222 ] [Tf _2中]的系统，对映体选择性ee的参数对（S） -CHBE为99.4％N] /甲醇/水相。在甲醇/水实验的情况下，ee参数达到92.5％。对于乙醇/水，ee为91.8％。的（R） - 在[N _8,222 ] [Tf ₂ N] /甲醇/水相中，在408 K下，ee达到99.3％，ee达到（S） -Ru-BINAP的CHBE异构体。对于导致（S） -CHBE的表观活化能的反应被评估。对于MeOH /水和EtOH /水，它们相似（110.5和110.7kJ.mol ^-1）。与[N _8,222 ] [Tf ₂ N] / MeOH /水系统相对应的表观活化能要高得多（约90 kJ.mol ^-1），达到200 kJ.mol ^-1的水平。。从与乙酰乙酸甲酯的氢化（MAA，〜200kJ.mol ^-1）的比较中可以看出，主要反应物的分子结构的影响可以忽略。[N _8,222 ] [Tf ₂ N]离子液体的存在对活化能之和的影响。通过使用手性化合物与手性溶剂化剂的对映选择性络合的方法的核磁共振另外评估了对映选择性合成的有效性。