Method for preparing levoterbutaline using chiral auxiliary

Abstract

To provide a method for preparing levoterbutaline using a chiral auxiliary. SOLUTION: A method for preparing L-terbutaline using chiral auxiliary, which uses S-(-)-tert-butylsulfinamide as raw material, reacts with 2-bromo-2-methylpropane and 3,5-dibenzyloxybromoacetophenone in sequence to obtain compound 5; reduces compound 5 under quaternary ammonium salt catalyst to obtain compound 6; removes tert-butylsulfinyl protection from compound 6 to obtain compound 7, which is hydrogenolyzed with alcohol solvent in the presence of palladium catalyst and hydrochloric acid to obtain L-terbutaline. The method is simple and reliable, the preparation cost is low, and the ee of the chiral product reaches 99.9%.

Description

[Technical field]

[0001] The present invention belongs to the field of pharmaceutical technology, specifically relates to a chiral preparation method for L-terbutaline. [Background technology]

[0002] Terbutaline is a fast-acting, short-acting adrenal receptor agonist that can selectively activate β2 receptors, relax bronchial smooth muscle, inhibit the release of endogenous spasmodic substances, and suppress endogenous transmitters and mucociliary activation, thereby relieving edema caused by activation (Non-Patent Document 1: Kyeong HK, Hyun JK, Seon-Pyo H., Sang DS, Arch. Pharm. Res. 2000, 23:441-445). Clinically, it is mainly used to treat bronchial asthma, asthmatic bronchitis, emphysema, and bronchial spasms in chronic obstructive pulmonary disease. Terbutaline has a chiral center of a secondary alcohol, but all of the compounds currently used in clinical practice are racemic. Research has shown that the levo isomer of terbutaline is the active ingredient that exerts its medicinal effects (Non-Patent Document 2: J. Med. Chem., 1972, 15, 1182-1183), while the dextro isomer is not only ineffective but also has toxic side effects. Therefore, researching methods for preparing L-terbutaline and re-marketing such a levo isomer has important clinical application value. For example, CN110156614 discloses that when comparing levo(-)terbutaline with the commercially available racemate, the anti-asthmatic efficacy is doubled, providing a new and preferable treatment method for asthma-related diseases.

[0003] The disclosed methods for preparing L-terbutaline are mainly as follows: 1. Decomposition method. Using tartaric acid or tartaric acid derivatives to decompose racemized terbutaline is the simplest and most intuitive method for preparing L-terbutaline (Patent Documents 1-2: CN1273966A, CN201810147612. 1). However, such methods often require multiple crystallizations to achieve satisfactory enantiomeric purity, the overall process is complicated, the yield is low, and at least half of the product is wasted, which does not meet the currently advocated principle of environmentally friendly chemistry.

[0004] 2. Enzymatic method: The enzymatic reduction method is a common method for preparing chiral secondary alcohols from prochiral ketones, but it requires the selection of an optimal enzyme catalyst and often has defects such as low reduction efficiency (Non-Patent Document 3: Journal of Molecular Catalysis B: Enzymatic, 84, (2012), 83-88).

[0005] 3. The reduction of prochiral ketones with borane in the presence of a chiral catalyst (Corey-Bakshi-Shibata catalyst or similar) has the drawbacks of toxicity of borane and difficult post-treatment, making it difficult to realize industrialized production.

[0006] 4. The asymmetric reduction of chloroacetophenone is realized by the transfer hydrogenation method of chiral ruthenium catalyst to obtain an important intermediate for the synthesis of L-terbutaline (Non-Patent Document 4: Chem. Pharm. Bull. 65, (2017), 389-395). This method uses expensive precious metals, and the ee of the product is only 91%, which cannot meet the requirements.

[0007] Due to various deficiencies in the prior art, it is of great significance to develop a new method for preparing L-terbutaline that is simple, efficient and low-cost. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] China 1273966A [Patent Document 2] China 201810147612 [Non-patent literature]

[0009] [Non-Patent Document 1] Kyeong HK, Hyun JK, Seon-Pyo H., Sang DS, Arch. Pharm. Res. 2000, 23:441-445 [Non-Patent Document 2] J. Med. Chem., 1972, 15, 1182-1183 [Non-Patent Document 3] Journal of Molecular Catalysis B: Enzymatic, 84, (2012), 83 - 88 [Non-Patent Document 4] Chem. Pharm. Bull. 65, (2017), 389-395 Summary of the Invention [Problem to be solved by the invention]

[0010] The objective of the present invention is to provide a method for preparing L-terbutaline; the method is simple and reliable, the preparation cost is low, and the ee of the chiral product reaches 99.9%. [Means for solving the problem]

[0011] The technical solution of the present invention is as follows: a method for preparing L-terbutaline using an asymmetric auxiliary, in the presence of palladium catalyst and hydrochloric acid, compound 7 is hydrogenolyzed with alcohol solvent to obtain L-terbutaline; wherein the chemical structure of compound 7 is as follows:

[0012] [ka] The chemical structure of L-terbutaline is:

[0013] [ka]

[0014] In the above technical solution, the palladium catalyst is a palladium carbon catalyst; the alcohol solvent is a low molecular weight alcohol, preferably methanol. Specifically, compound 7 is dissolved in methanol, palladium carbon catalyst is added, hydrochloric acid is dripped in, hydrogenolysis is carried out under normal pressure hydrogen for 1-3 hours, palladium carbon is removed by filtration, the filtrate is distilled under reduced pressure, and the remaining solid is crystallized to obtain the product L-terbutaline hydrochloride 8.

[0015] In the present invention, S-(-)-tert-butylsulfinamide is used as the raw material, which is reacted with 2-bromo-2-methylpropane and 3,5-dibenzyloxybromoacetophenone in sequence to obtain compound 5; compound 5 is reduced under a quaternary ammonium salt catalyst to obtain compound 6; compound 6 is protected by removing tert-butylsulfinyl to obtain intermediate 7. The specific steps and the structural formula of the compound are as follows: (1) Prepare tert-butylsulfinamide-substituted acetophenone intermediate (compound 5). tert-Butylsulfinamide 1 is dissolved in an organic solvent, an alkali is added, then 2-bromo-2-methylpropane is added dropwise, and the mixture is reacted at 0-60°C for 2-5 hours, and then 3,5-dibenzyloxybromoacetophenone 4 is added, and the mixture is reacted at 30-80°C for 2-8 hours; After the reaction is completed, the mixture is filtered to remove solid substances, and then the mixture is distilled under reduced pressure to remove the solvent, to obtain compound 5, which is directly used in the next reaction; The organic solvent is acetonitrile, THF, DMF, acetone, toluene or ethyl acetate, preferably acetonitrile, THF and DMF, and more preferably acetonitrile; The alkali is potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, potassium phosphate, potassium fluoride, sodium hydride or potassium tert-butoxide, preferably potassium carbonate and sodium carbonate, and more preferably potassium carbonate; The reaction is as follows:

[0016] [ka] (2) The ketone is reduced to a chiral alcohol (compound 6) under the control of chiral tert-butylsulfinamide. Compound 5 is dissolved in a solvent, a quaternary ammonium salt is added, and then sodium borohydride is added in several portions within 1 to 2 hours at 0 to 10°C. After completion, the mixture is stirred for 1 hour, and then an aqueous ammonium chloride solution is added to quench the mixture, extracted, dried, distilled under reduced pressure, and the remaining solid is crystallized using ethanol to obtain compound 6; the organic solvent is one or more of THF, ethanol, methanol, and isopropanol, and is preferably a mixed solvent of THF and isopropanol; the quaternary ammonium salt is tetrabutylammonium bromide, tetrabutylammonium chloride, tetrapropylammonium bromide, tetrapropylammonium bromide, or triethylbenzylammonium bromide, and is preferably tetrabutylammonium bromide and tetrabutylammonium chloride, and more preferably tetrabutylammonium bromide; the reaction is as shown below.

[0017] [ka]

[0018] (3) The tert-butylsulfinyl protection is removed to obtain an intermediate (compound 7). Compound 6 is dissolved in methanol, concentrated hydrochloric acid is added, and the reaction is carried out at 0-60°C for 2-5 hours. The solvent is removed by distillation under reduced pressure, and the residue is added with saturated sodium bicarbonate solution, extracted with an organic solvent, dried, and distilled under reduced pressure to obtain compound 7, which is used directly in the next reaction. The reaction is as shown below.

[0019] [ka]

[0020] (4) The benzyl protection is removed to obtain the target product L-terbutaline. Compound 7 is dissolved in methanol, palladium carbon catalyst is added, hydrochloric acid is added dropwise, hydrogenolysis is performed under normal pressure hydrogen for 1 to 3 hours, palladium carbon is removed by filtration, the filtrate is distilled under reduced pressure, and the remaining solid is crystallized to obtain R-terbutaline hydrochloride 8. The reaction is as shown below.

[0021] [ka] Effect of the Invention

[0022] To implement the above technical solution, the present invention has the following advantages over the prior art: the present invention first uses the commercialized inexpensive chiral source tert-butylsulfinamide as a prosthetic group to control the asymmetric reduction of ketones, and the small amount of non-enantiomers can be easily removed by crystallization, and the ee of the product reaches 99.9%; the operation of the entire process is very simple, and the reagents used are all inexpensive, readily available, and non-toxic, which is very suitable for industrial production. [Brief description of the drawings]

[0023] [Figure 1]FIG. 1 is a nuclear magnetic hydrogen spectrum of the hydrochloride salt of R-terbutaline prepared in Example 1. [Diagram 2] FIG. 2 is a nuclear magnetic carbon spectrum of the hydrochloride salt of R-terbutaline prepared in Example 1. [Diagram 3] FIG. 3 is a mass spectrum of the hydrochloride salt of R-terbutaline prepared in Example 1. [Figure 4] FIG. 4 is a liquid chromatogram of the hydrochloride salt of R-terbutaline prepared in Example 1. [Diagram 5] Figure 5 is a liquid chromatogram of conventional racemic terbutaline (Hiromori Pharmaceutical). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] The specific preparation and testing methods of the present invention are general methods, such as general liquid chromatogram (HPLC+chiral column) to test the purity and ee value. The present invention will be described in more detail below with reference to the following examples.

[0025] The preparation method of the present invention is shown as follows:

[0026] [ka]

[0027] Example 1.

[0028] S-(-)-tert-butylsulfinamide 1 (14.8g, 110mmol) was dissolved in acetonitrile (300mL), potassium carbonate (18.0g, 130mmol) was added, then 2-bromo-2-methylpropane (17.8g, 130mmol) was added dropwise, and the mixture was heated to 50℃ for 4 hours, followed by addition of 3,5-dibenzyloxybromoacetophenone 4 (41.1g, 100mmol), followed by heating at 60℃ for 6 hours. After the reaction was completed, the solid material was removed by filtration, and the solvent was removed by distillation under reduced pressure to obtain compound 5, which was directly used in the next reaction.

[0029] The compound 5 obtained above was dissolved in a mixed solvent of THF (200mL) and isopropanol (200mL), and tetrabutylammonium bromide (3.22g, 10mmol) was added, and the reaction system was cooled to 0℃. Then, sodium borohydride (3.02g, 80mmol) was uniformly added in three portions within 1.5 hours. After the conversion was completed, the mixture was stirred at 0℃ for 1 hour, and quenched by adding aqueous ammonium chloride solution (50mL). The mixture was extracted with ethyl acetate, and the extracts were combined, dried over sodium sulfate, and distilled under reduced pressure. The remaining solid was crystallized from ethanol (90mL) to obtain 37.1g of white solid compound 6, with a two-step yield of 71%.

[0030] Compound 6 (26.1 g, 50 mmol) was dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) was added, and the mixture was reacted at 50° C. for 3 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the residue was added with saturated sodium bicarbonate solution (80 mL), and extracted three times with ethyl acetate. The organic layers were combined, dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure to obtain compound 7, which was directly used in the next reaction.

[0031] The compound 7 obtained above was dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) was added, 2 mol / L hydrogen chloride methanol solution (25 mL) was added dropwise, and then hydrogenolysis was performed under normal pressure hydrogen for 2 hours, followed by filtration to remove palladium carbon, and the filtrate was subjected to general vacuum distillation to remove the solvent, and the remaining solid was crystallized from tetrahydrofuran (100 mL) to obtain a total of 11.7 g of R-terbutaline hydrochloride 8, with a two-step yield of 85%, a purity of 99.7%, an ee of 99.9%, and an optical rotation [a] D20 = -39.2 (c =1.0 in MeOH).

[0032] Example 2.

[0033] Based on Example 1, potassium carbonate (18.0 g, 130 mmol) was replaced with sodium carbonate (130 mmol), and the rest was left unchanged to obtain R-terbutaline hydrochloride salt 8 with a purity of 99.6% and an ee of 99.7%.

[0034] Based on Example 1, tetrabutylammonium bromide (3.22 g, 10 mmol) was changed to tetrabutylammonium chloride (10 mmol), and the rest was unchanged to obtain R-terbutaline hydrochloride salt 8 with a purity of 99.5% and an ee of 99.1%.

[0035] Based on Example 1, isopropanol (200 mL) was replaced with ethanol (200 mL), and the rest was left unchanged to obtain R-terbutaline hydrochloride salt 8 with a purity of 99.1% and an ee of 99.2%.

[0036] Comparative Example 1.

[0037] Based on Example 1, omitting tetrabutylammonium bromide and remaining unchanged, the two-step yield of compound 6 is 55% and further the hydrochloride salt of R-terbutaline 8 is obtained with an ee of 95.2%.

[0038] Based on Example 1, the mixed solvent of THF (200 mL) and isopropanol (200 mL) was changed to isopropanol (400 mL), and the rest was unchanged. The yield of compound 6 in two steps was 60%, and further R-terbutaline hydrochloride 8 was prepared with an ee of 98.8%.

[0039] Based on Example 1, sodium borohydride (3.02 g, 80 mmol) was changed to potassium borohydride (80 mmol), and the rest was unchanged. The two-step yield of compound 6 was 59%, and further R-terbutaline hydrochloride 8 was prepared with an ee of 98.3%.

[0040] Example 3.

[0041] S-(-)-tert-butylsulfinamide 1 (14.8g, 110mmol) was dissolved in acetonitrile (300mL), potassium carbonate (18.0g, 130mmol) was added, then 2-bromo-2-methylpropane (17.8g, 130mmol) was added dropwise, and the mixture was heated to 40℃ for 3 hours, followed by addition of 3,5-dibenzyloxybromoacetophenone 4 (41.1g, 100mmol), followed by reaction at 60℃ for 6 hours. After the reaction was completed, the solid material was removed by filtration, and then the solvent was removed by distillation under reduced pressure to obtain compound 5, which was directly used in the next reaction.

[0042] The compound 5 obtained above is dissolved in a mixed solvent of THF (200 mL) and isopropanol (200 mL), tetrabutylammonium bromide (3.22 g, 10 mmol) is added, the reaction system is cooled to 0° C., and then sodium borohydride (3.02 g, 80 mmol) is uniformly added in three portions within 1.5 hours. After the addition is completed, the mixture is stirred at 0° C. for 1 hour, quenched by adding an aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate, the extracts are combined, dried over sodium sulfate, distilled under reduced pressure, and the remaining solid is crystallized from ethanol (90 mL) to obtain a white solid compound 6.

[0043] Compound 6 (26.1 g, 50 mmol) was dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) was added, and the mixture was reacted at 50° C. for 3 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the residue was added with saturated sodium bicarbonate solution (80 mL), and extracted three times with ethyl acetate. The organic layers were combined, dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure to obtain compound 7, which was directly used in the next reaction.

[0044] The compound 7 obtained above is dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) is added, 2 mol / L hydrogen chloride methanol solution (25 mL) is added dropwise, and then hydrogenolysis is performed under normal pressure hydrogen for 2 hours, followed by filtration to remove the palladium carbon, and the filtrate is subjected to general vacuum distillation to remove the solvent, and the remaining solid is crystallized from tetrahydrofuran (100 mL) to obtain R-terbutaline hydrochloride salt 8.

[0045] Example 4.

[0046] S-(-)-tert-butylsulfinamide 1 (14.8g, 110mmol) was dissolved in acetonitrile (300mL), potassium carbonate (18.0g, 130mmol) was added, then 2-bromo-2-methylpropane (17.8g, 130mmol) was added dropwise, and the mixture was heated to 50℃ for 4 hours, followed by addition of 3,5-dibenzyloxybromoacetophenone 4 (41.1g, 100mmol), followed by heating at 60℃ for 6 hours. After the reaction was completed, the solid material was removed by filtration, and the solvent was removed by distillation under reduced pressure to obtain compound 5, which was directly used in the next reaction.

[0047] The obtained compound 5 is dissolved in a mixed solvent of THF (200 mL) and isopropanol (200 mL), tetrabutylammonium bromide (3.22 g, 10 mmol) is added, the reaction system is cooled to 5° C., and then sodium borohydride (3.02 g, 80 mmol) is uniformly added in two portions within 1 hour. After the addition is completed, the mixture is stirred at 0° C. for 1 hour, quenched by adding an aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate, the extracts are combined, dried over sodium sulfate, distilled under reduced pressure, and the remaining solid is crystallized from ethanol (90 mL) to obtain a white solid compound 6.

[0048] Compound 6 (26.1 g, 50 mmol) was dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) was added, and the mixture was reacted at 50° C. for 3 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the residue was added with saturated sodium bicarbonate solution (80 mL), and extracted three times with ethyl acetate. The organic layers were combined, dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure to obtain compound 7, which was directly used in the next reaction.

[0049] The compound 7 obtained above is dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) is added, 2 mol / L hydrogen chloride methanol solution (25 mL) is added dropwise, and then hydrogenolysis is performed under normal pressure hydrogen for 2.5 hours, followed by filtration to remove the palladium carbon. The filtrate is subjected to general reduced pressure distillation to remove the solvent, and the remaining solid is crystallized in tetrahydrofuran (100 mL) to obtain R-terbutaline hydrochloride salt 8.

[0050] Example 5.

[0051] S-(-)-tert-butylsulfinamide 1 (14.8g, 110mmol) was dissolved in acetonitrile (300mL), potassium carbonate (18.0g, 130mmol) was added, then 2-bromo-2-methylpropane (17.8g, 130mmol) was added dropwise, and the mixture was heated to 50℃ for 4 hours, followed by addition of 3,5-dibenzyloxybromoacetophenone 4 (41.1g, 100mmol), followed by heating at 60℃ for 6 hours. After the reaction was completed, the solid material was removed by filtration, and the solvent was removed by distillation under reduced pressure to obtain compound 5, which was directly used in the next reaction.

[0052] The obtained compound 5 is dissolved in a mixed solvent of THF (200mL) and isopropanol (200mL), tetrabutylammonium bromide (3.22g, 10mmol) is added, the reaction system is cooled to 0℃, and then sodium borohydride (3.02g, 80mmol) is uniformly added in three portions within 1.5 hours. After the conversion is completed, the mixture is stirred at 0℃ for 1 hour, quenched by adding aqueous ammonium chloride solution (50mL), extracted with ethyl acetate, the extracts are combined, dried over sodium sulfate, distilled under reduced pressure, and the remaining solid is crystallized from ethanol (90mL) to obtain white solid compound 6.

[0053] Compound 6 (26.1 g, 50 mmol) was dissolved in methanol (150 mL), and concentrated hydrochloric acid (12.5 mL, 37.5 wt%) was added. The mixture was reacted at 50° C. for 4 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure. Saturated sodium bicarbonate solution (80 mL) was added to the residue, and the mixture was extracted three times with ethyl acetate. The organic layers were combined, dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure to obtain compound 7, which was directly used in the next reaction.

[0054] The compound 7 obtained above is dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) is added, and the mixture is subjected to hydrogenolysis with 2 mol / L hydrogen chloride methanol solution (25 mL) and then atmospheric hydrogen pressure for 2 hours. The mixture is then filtered to remove the palladium carbon, and the filtrate is subjected to general vacuum distillation to remove the solvent. The remaining solid is crystallized in tetrahydrofuran (100 mL) to obtain R-terbutaline hydrochloride salt 8.

[0055] Example 6.

[0056] S-(-)-tert-butylsulfinamide 1 (14.8 g, 110 mmol) was dissolved in acetonitrile (300 mL), potassium carbonate (18.0 g, 130 mmol) was added, then 2-bromo-2-methylpropane (17.8 g, 130 mmol) was added dropwise, and the mixture was heated to 50° C. for 4 hours, followed by addition of 3,5-dibenzyloxybromoacetophenone 4 (41.1 g, 100 mmol), followed by reaction at 60° C. for 6 hours. After the reaction was completed, the solid material was removed by filtration, and then the solvent was removed by distillation under reduced pressure to obtain compound 5, which was directly used in the next reaction.

[0057] The obtained compound 5 is dissolved in a mixed solvent of THF (200 mL) and isopropanol (200 mL), tetrabutylammonium bromide (3.22 g, 10 mmol) is added, the reaction system is cooled to 0° C., and then sodium borohydride (3.02 g, 80 mmol) is uniformly added in three portions within 1.5 hours. After the conversion is completed, the mixture is stirred at 0° C. for 1 hour, quenched by adding aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate, the extracts are combined, dried over sodium sulfate, distilled under reduced pressure, and the remaining solid is crystallized from ethanol (90 mL) to obtain white solid compound 6.

[0058] Compound 6 (26.1 g, 50 mmol) was dissolved in methanol (150 mL), concentrated hydrochloric acid (12.5 mL, 37.5 wt%) was added, and the mixture was reacted at 50° C. for 3 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure, and the residue was added with saturated sodium bicarbonate solution (80 mL), and extracted three times with ethyl acetate. The organic layers were combined, dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure to obtain compound 7, which was directly used in the next reaction.

[0059] The compound 7 obtained above is dissolved in methanol (200 mL), 10 wt% palladium carbon catalyst (2.0 g) is added, 2 mol / L hydrogen chloride methanol solution (25 mL) is added dropwise, and then hydrogenolysis is performed under normal pressure hydrogen for 2.5 hours, followed by filtration to remove the palladium carbon. The filtrate is subjected to general reduced pressure distillation to remove the solvent, and the remaining solid is crystallized in tetrahydrofuran (100 mL) to obtain R-terbutaline hydrochloride salt 8.

[0060] The method provided by the present invention uses inexpensive and readily available chiral tert-butylsulfinamide as a chiral auxiliary to control the chiral secondary alcohol required for asymmetric reduction of ketones, and the chiral auxiliary can be removed under simple acidic conditions.

Claims

1. The following compound 7: [Formula 1] And Compound 7 is hydrogenolyzed in an alcohol solvent in the presence of a palladium catalyst and hydrochloric acid; L-Terbutaline as follows: [chemical 2] Get A method for preparing L-terbutaline using a chiral auxiliary, comprising:

2. Using S-(-)-tert-butylsulfinamide as a chiral auxiliary as a raw material, the compound is reacted with 2-bromo-2-methylpropane and 3,5-dibenzyloxybromoacetophenone in this order to obtain the following compound 5: [C3] And Compound 5 is hydrogenated in the presence of a quaternary ammonium salt and reduced to give compound 6: [C4] And Removal of the tert-butylsulfinyl protection of compound 6 gives compound 7. A method for preparing L-terbutaline using the chiral auxiliary of claim 1.

3. Dissolve tert-butylsulfinamide in an organic solvent, add an alkali, then dropwise add 2-bromo-2-methylpropane, react at 0-60°C for 2-5 hours, add 3,5-dibenzyloxybromoacetophenone, and continue reacting at 30-80°C for 2-8 hours to obtain compound 5. A method for producing L-terbutaline using the chiral auxiliary of claim 2.

4. Compound 5 is dissolved in a solvent, a quaternary ammonium salt is added, and then sodium borohydride is added at 0 to 10° C. to carry out a reduction reaction to obtain compound 6. A method for preparing L-terbutaline using the chiral auxiliary of claim 2.

5. Compound 6 is dissolved in an alcohol solvent, concentrated hydrochloric acid is added, and the mixture is reacted at 0 to 60° C. for 2 to 5 hours to obtain compound 7. A method for preparing L-terbutaline using the chiral auxiliary of claim 2.

6. the palladium catalyst is an inorganic palladium catalyst; The alcohol solvent is methanol A method for preparing L-terbutaline using the chiral auxiliary of claim 1.

7. the palladium catalyst is a palladium on carbon catalyst; The alcohol solvent is methanol A method for preparing L-terbutaline using the chiral auxiliary of claim 6.

8. Compound 7 is dissolved in an alcohol solvent, a palladium catalyst is added, hydrochloric acid is added dropwise, and the compound is hydrogenolyzed under normal pressure of hydrogen for 1 to 3 hours to obtain the product L-terbutaline. A method for preparing L-terbutaline using the chiral auxiliary of claim 1.

9. Use of S-(-)-tert-butylsulfinamide in the preparation of L-terbutaline.

10. The structural formula: [C5] Used for L-terbutaline having A compound characterized by:

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