Preparation method of gliclazide intermediate 1, 2-cyclopentanedimethanol

Abstract

The invention discloses a preparation method of gliclazide intermediate 1, 2-cyclopentanediol.The preparation method comprises the steps that dicyclopentadiene serves as a raw material, and the product is obtained through depolymerization, [2 + 2] cycloaddition, ring opening, hydrolysis, reduction, hydrogenation or re-reduction reaction in sequence. The raw materials used in the method are low in price and wide in source, the reaction conditions of each step are mild, the process is simple, the production cost is reduced, and the method has very high application value.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical chemical industry, and specifically relates to a preparation method of a gliclazide intermediate. Background Art

[0002] As a second-generation sulfonylurea drug, gliclazide regulates ion channels on the surface of pancreatic cells, thereby promoting the synthesis and secretion of insulin, and ultimately achieving the effect of lowering blood sugar.

[0003] However, the original production process is costly and produces toxic impurities, so improving the process has become a new direction for research on this type of subject.

[0004] The existing process for preparing the gliclazide intermediate 1,2-cyclopentyl dimethanol generally adopts esterification followed by reduction of 1,2-cyclopentanedicarboxylic acid. Patents (CN 102993080 A) and literature (China Journal of Pharmaceutical Industry. 2017;48(2):154-156) all adopt this method. However, the raw material 1,2-cyclopentanedicarboxylic acid in this method is expensive and difficult to obtain, and the reducing agent lithium aluminum tetrahydride is expensive and sensitive to water, which makes it impossible to achieve industrial production. Summary of the invention

[0005] In view of the existing defects and problems, the present invention provides a method for preparing 1,2-cyclopentanedimethanol which has simple process, low cost and is easy to operate.

[0006] The technical solution adopted by the present invention is as follows: The present invention provides a method for preparing a gliclazide intermediate compound of formula A-1 or formula A-2, which is prepared by a reduction reaction of a compound of formula VI, and the reaction equation is: .

[0007] Furthermore, the reducing agent for the reduction reaction is a boron reducing agent, which can be selected from sodium borohydride, lithium borohydride, potassium borohydride, sodium cyanoborohydride, and sodium triacetoxyborohydride.

[0008] Wherein, the reduction reaction solvent is an organic solvent, preferably tetrahydrofuran.

[0009] Wherein, the mass ratio of the raw material compound VI to the solvent in the reduction reaction for preparing the compound A-1 is in the range of 1:8 to 9.9.

[0010] The present invention provides a method for preparing a compound of formula I-1 or a compound of formula I-2, which is further prepared by hydrogenating a compound of formula A-1 or A-2, and the reaction equation is as follows: .

[0011] Furthermore, in the preparation method of the compound of formula I-1, the catalyst used in the hydrogenation reaction is one or more of Pd / C and skeleton nickel, preferably Pd / C; the hydrogen source used is hydrogen, formic acid or ammonium formate.

[0012] Wherein, the hydrogenation reaction solvent is an ether solvent or an ester solvent, and ethyl acetate is more preferred.

[0013] The mass ratio of the raw material compound A-1 to the solvent in the hydrogenation reaction is in the range of 1:5-15, preferably 1:8-9.

[0014] Furthermore, the hydrogenation reaction step in the preparation method of the compound of formula I-2 includes reacting a compound of formula A-2, formic acid, and 10% Pd / C to prepare a compound of formula I-2.

[0015] Wherein, the reaction time of the hydrogenation reaction is 15 to 25 hours.

[0016] The present invention also provides a method for preparing 1,2-cyclopentane dimethanol, an intermediate of gliclazide, using a compound of formula II as a starting material, and obtaining a compound of formula VI through depolymerization reaction, [2+2] cycloaddition, ring opening, and hydrolysis reaction. The compound of formula VI is further subjected to reduction, hydrogenation reaction or reduction, hydrogenation, and reduction reaction to obtain a compound of formula I-1. The reaction formula is as follows: .

[0017] Wherein, the reaction temperature of the depolymerization reaction is 100~200℃.

[0018] Wherein, the reaction reagent of the [2+2] cycloaddition is dichloroacetyl chloride.

[0019] The reaction temperature of the [2+2] cycloaddition is 20-30°C, and the preferred temperature is 25-30°C.

[0020] Among them, the treatment process after the ring-opening reaction is: adding acid at 0°C to adjust the pH to acidic, keeping warm for 2 hours after the addition is completed, filtering to obtain a light yellow solid, and the solid is recrystallized with petroleum ether and then dried to obtain the fine formula V compound 2-(dichloromethyl)cyclopent-3-ene-1-carboxylic acid.

[0021] Wherein, the acid used for adjusting pH in the treatment process after the ring-opening reaction is concentrated hydrochloric acid.

[0022] Wherein, the reaction temperature of the hydrolysis reaction is 50~120℃.

[0023] The raw materials used in the invention are cheap and widely available, and the reaction conditions in each step are mild, the process is simple, the production cost is reduced, the application value is high, the expensive and highly toxic reaction reagents in the original process route are avoided, and the invention is more suitable for large-scale industrial production. DETAILED DESCRIPTION

[0024] In order to further understand the present invention, the preparation method of a gliclazide intermediate 1,2-cyclopentanedicarbinol provided by the present invention is described in detail below in conjunction with the examples. It should be understood that these examples are only for further illustrating the features of the present invention in detail, and are not intended to limit the scope of the present invention or the scope of the claims of the present invention.

[0025] Example 1 A. Preparation of Cyclopentadiene (III) In a reactor equipped with a stirring and heating device, add dicyclopentadiene (30 g, 0.2 mol), set up a distillation device, heat to 180 ° C and distill and depolymerize for 10-15 hours. A colorless liquid is obtained in the receiving bottle, which is cyclopentadiene (III), about 27 g, and the yield is about 90.1%; B. Preparation of 7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one (IV) Cyclopentadiene (III) (20 g, 0.3 mol) and n-hexane 200 ml were added to the reactor, and 30.6 g of triethylamine was added after stirring evenly. The mixture was then placed in an ice bath and cooled to 0°C. Then 44.6 g of dichloroacetyl chloride was slowly added dropwise. The temperature was kept below 5°C during the addition process. The mixture was then heated to 25-30°C and stirred for 8 hours. After the reaction was completed, the insoluble matter was removed by filtration. The filtrate was distilled under reduced pressure and the solvent was removed to obtain about 45.6 g of brown-red liquid 7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one (IV). The yield was about 86.6%. 1 HNMR (400 MHz, CDCl3) d (ppm): 6.04 (dq, J = 6.0, 2.1 Hz,1H), 5.80 (dq, J = 4.9, 2.3 Hz, 1H), 4.26 (ddd, J = 8.8, 7.4, 1.2 Hz, 1H), 4.07(dp, J = 7.2, 2.1 Hz, 1H), 2.81 (ddt, J = 17.3, 3.9, 2.0 Hz, 1H), 2.64 – 2.51(m, 1H). EI-MS:m / z[M] +175.9806, [M+4] + 179.9732 C. Preparation of 2-(dichloromethyl)cyclopent-3-ene-1-carboxylic acid (V) Add 200 ml of 20% sodium hydroxide aqueous solution to the reactor, stir evenly and cool to 0°C in an ice bath, then slowly drop 7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one (IV) (20 g, 0.1 mol), the drop time is controlled within 1 hour, and the temperature is kept above 3°C during the drop process. After the drop is complete, react at 0°C for 0.5 hour, then drop concentrated hydrochloric acid (38 ml) at 0°C to adjust the pH to acidic. After the drop is complete, keep warm for 2 hours for crystallization, and filter to obtain a light yellow solid. The solid is recrystallized from petroleum ether and dried to obtain about 19.36 g of fine 2-(dichloromethyl)cyclopent-3-ene-1-carboxylic acid (V), with a yield of about 87.9%. Melting point: 90.0~91.9°C. 1 H NMR (400 MHz, CDCl3) d (ppm): 11.11 (s, 1H), 6.35 (d, J = 5.0Hz, 1H), 6.08 (dq, J = 6.3, 2.2 Hz, 1H), 5.88 (dq, J = 6.3, 2.2 Hz, 1H), 3.71(ddt, J = 9.1, 5.0, 2.5 Hz, 1H), 3.40 (td, J = 9.1, 7.6 Hz, 1H), 2.86 (ddq, J =16.9, 7.6, 2.5 Hz, 1H), 2.70 – 2.59 (m, 1H). EI-MS:m / z[M] + 193.9898, [M+4] + 197.9843 D. Preparation of 2-Formylcyclopent-2-ene-1-carboxylic acid (VI) 2-(Dichloromethyl)cyclopent-3-ene-1-carboxylic acid (V) (20 g, 0.1 mol) and 100 ml of water were added to a stirred reactor, and then the temperature was raised to 100°C for reaction for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and ethyl acetate was added for extraction. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove the desiccant, and the solvent was removed by distillation under reduced pressure to obtain about 12.2 g of 2-formylcyclopent-2-ene-1-carboxylic acid (VI) with a yield of about 87.6%. 1 H NMR (400 MHz, CDCl3) d (ppm):10.05 (d, J = 85.2 Hz, 1H), 9.73 (s, 1H), 7.06 (q, J = 2.4 Hz, 1H), 3.75 (ddt, J = 9.1, 5.3, 1.9 Hz, 1H), 2.87 – 2.56 (m, 2H), 2.47 – 2.16 (m, 2H). ESI-MS (m / z): 139.0 (MH) E. Preparation of cyclopent-2-ene-1,2-diyldimethanol (A-1) 2-Formylcyclopent-2-ene-1-carboxylic acid (VI) (15 g, 0.1 mol) and 150 ml of tetrahydrofuran were added to the reactor, followed by the addition of 20.7 g of N,N-carbonyldiimidazole. After reacting for 1 hour, 37.5 ml of water was added, followed by cooling to 0 °C in an ice bath, and sodium borohydride was added in four batches, 3.1 g in each batch. After the addition was completed, the temperature was raised to room temperature and reacted for 6 hours, and then 108 ml of 3.6% dilute hydrochloric acid was added to quench, and most of the organic solvent was distilled off. Then, ethyl acetate was used for extraction, and the organic layer was dried over anhydrous magnesium sulfate, and the desiccant was filtered out. Finally, ethyl acetate was distilled off to obtain about 10.8 g of cyclopent-2-ene-1,2-diyl dimethanol (A-1), with a yield of about 85.0%. 1 H NMR (400 MHz, CDCl3) d (ppm): 5.73(t, J = 2.1 Hz, 1H), 4.29 (d, J = 12.4 Hz. 1H). 4.13(dg, J =12.3, 1.2 Hz, 1H),3.72 (dd, J =10.6, 4.4Hz, 1H), 3.50 (dd, J = 10.6, 8.2 Hz, 1H). 3.17(s, 2H),2.92-2.80(m, 1H), 2.41-2.19 (m, 2H), 2.18-2.01 (m, 1H), 1.57 (ddt, J = 12.8,9.0, 6.3 Hz, 1H). ESI-MS (m / z): 151.1 (M+Na) F. Preparation method 1 of 1,2-cyclopentyl dimethanol (I-1) Cyclopent-2-ene-1,2-diyldimethanol (A-1) (15 g, 0.1 mol) and 150 ml of ethyl acetate were added to the reactor, followed by 1.06 g of 5% Pd / C. Hydrogen was introduced at room temperature and atmospheric pressure to react for 24 hours. After the reaction, the catalyst was filtered out and the solvent was distilled off to obtain about 14.5 g of 1,2-cyclopentyldimethanol (I-1) with a yield of about 95.1%. 1 H NMR (400 MHz, CDCl3) d (ppm): 4.59 – 3.89 (m, 2H), 3.63 (dd, J = 11.2, 9.1 Hz, 2H),3.56 (dd, J = 11.2, 3.8 Hz, 2H), 2.25 (tt, J = 7.7, 4.2 Hz, 2H), 1.77 – 1.67(m, 2H), 1.60 (dtt, J = 11.8, 7.8, 3.6 Hz, 1H), 1.51 – 1.40 (m, 1H), 1.17 (dq, J = 13.0, 8.1 Hz, 2H). ESI-MS (m / z): 153.1 (M+Na) G. Preparation method 2 of 1,2-cyclopentyl dimethanol (I-1) Cyclopent-2-ene-1,2-diyldimethanol (A-1) (15 g, 0.1 mol) and tetrahydrofuran 150 ml were added to the reactor, followed by the addition of skeletal nickel catalyst 1.5 g. Hydrogen was introduced at room temperature and atmospheric pressure to react for 30 hours. After the reaction, the catalyst was filtered out and the solvent was distilled off to obtain about 14.3 g of 1,2-cyclopentyldimethanol (I-1) with a yield of about 93.8%. 1 H NMR (400 MHz, CDCl3) d (ppm): 4.59 – 3.89 (m, 2H), 3.63 (dd, J = 11.2, 9.1 Hz, 2H),3.56 (dd, J = 11.2, 3.8 Hz, 2H), 2.25 (tt, J = 7.7, 4.2 Hz, 2H), 1.77 – 1.67(m, 2H), 1.60 (dtt, J = 11.8, 7.8, 3.6 Hz, 1H), 1.51 – 1.40 (m, 1H), 1.17 (dq, J= 13.0, 8.1 Hz, 2H). ESI-MS (m / z): 153.1 (M+Na) Example 2

[0026] The other steps are the same as those in Example 1, except that the preparation method of 2-formylcyclopent-2-ene-1-carboxylic acid (VI) in step D is as follows: 2-(Dichloromethyl)cyclopent-3-ene-1-carboxylic acid (V) (20 g, 0.1 mol) and 100 ml of water were added to a stirred reactor, followed by the addition of 5.3 g of sodium carbonate, and then the temperature was raised to 100 °C for reaction for 1 hour. After the reaction was completed, the mixture was cooled to room temperature, and then 10 ml of concentrated hydrochloric acid was added to adjust the pH to 1. Ethyl acetate was then added for extraction, and the organic layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove the desiccant, and the solvent was removed by distillation under reduced pressure to obtain about 11.9 g of 2-formylcyclopent-2-ene-1-carboxylic acid (VI) with a yield of about 85.0%. Example 3

[0027] The other steps are the same as those in Example 1, except that the preparation method of 2-formylcyclopent-2-ene-1-carboxylic acid (VI) in step D is as follows: 2-(Dichloromethyl)cyclopent-3-ene-1-carboxylic acid (V) (20 g, 0.1 mol) and 100 ml of water were added to a stirred reactor, followed by the addition of 8.4 g of sodium bicarbonate, and then the temperature was raised to 100 °C for 1 hour. After the reaction was completed, the mixture was cooled to room temperature, and then 10 ml of concentrated hydrochloric acid was added to adjust the pH to 1. Ethyl acetate was added for extraction, and the organic layer was separated. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove the desiccant, and the solvent was removed by distillation under reduced pressure to obtain about 12.3 g of 2-formylcyclopent-2-ene-1-carboxylic acid (VI) with a yield of about 87.8%. Example 4

[0028] The other steps are the same as those in Example 1, except that the preparation method of cyclopent-2-ene-1,2-diyldimethanol (A-1) in step E is as follows: Add 2-formylcyclopent-2-ene-1-carboxylic acid (VI) (15 g, 0.1 mol) and 150 ml of tetrahydrofuran to the reactor, then add 20.7 g of N,N'-carbonyldiimidazole, and react for 1 hour. Add 50 ml of tetrahydrofuran to another stirred reactor, then add 50 ml of water, then cool to 0 ° C in an ice bath, add 12.4 g of sodium borohydride, and after dissolving, add the above reaction solution dropwise to the sodium borohydride solution. During the dropwise addition, keep the temperature no higher than 5 ° C, and the dropwise addition time is controlled within 3 hours. After the dropwise addition is completed, keep the temperature for 8 hours. After the reaction is completed, add 108 ml of 3.6% dilute hydrochloric acid to quench, then distill off most of the organic solvent, extract with ethyl acetate, separate the liquids, dry the organic layer over anhydrous magnesium sulfate, filter to remove the desiccant, and finally distill off the ethyl acetate to obtain about 9.1 g of cyclopent-2-ene-1,2-diyl dimethanol (A-1), with a yield of about 71.0%. Example 5

[0029] The other steps are the same as those in Example 1, except that the preparation method of cyclopent-2-ene-1,2-diyldimethanol (A-1) in step E is as follows: 150 ml of tetrahydrofuran and 7.6 g of lithium aluminum hydride were added to the reactor, and then cooled to 0 °C in an ice bath. 2-Formylcyclopent-2-ene-1-carboxylic acid (VI) (15 g, 0.1 mol) was dissolved in 50 ml of tetrahydrofuran and added dropwise to the above solution. The temperature was kept below 5 °C during the addition process, and the addition time was within 1 hour. After the addition was completed, the reaction was kept warm for 8 hours. After the reaction was completed, 100 ml of water was added at 0 °C to quench, and then most of the organic solvent was distilled off, and then extracted with ethyl acetate, separated, the organic layer was dried over anhydrous magnesium sulfate, and the desiccant was filtered out. Finally, ethyl acetate was distilled off to obtain about 11.1 g of cyclopent-2-ene-1,2-diyldimethanol (A-1) with a yield of about 86.3%. Example 6

[0030] The other steps are the same as those in Example 1, except that the preparation method of 1,2-cyclopentyl dimethanol (I-1) in step F is as follows: 150 ml of formic acid was added to the reactor, followed by cyclopent-2-ene-1,2-diyldimethanol (A-1) (15 g, 0.1 mol), and finally 5% Pd / C 1.06 g. The reaction was carried out at room temperature and atmospheric pressure for 24 hours. After the reaction was completed, the catalyst was filtered out and the solvent was distilled off to obtain about 13.5 g of 1,2-cyclopentyldimethanol (I-1), with a yield of about 90.9%. Example 7

[0031] The other steps are the same as those in Example 1, except that the preparation method of 1,2-cyclopentyl dimethanol (I-1) in step F is as follows: 150 ml of methanol was added to the reactor, followed by cyclopent-2-ene-1,2-diyldimethanol (A-1) (15 g, 0.1 mol) and 1.06 g of 5% Pd / C, and finally 31.4 g of ammonium formate. The reaction was carried out at room temperature and normal pressure for 24 hours. After the reaction was completed, the catalyst was filtered out and the solvent was distilled off. The crude product was dissolved in dichloromethane, the precipitated solid was filtered, washed with dichloromethane, and finally distilled off dichloromethane under reduced pressure to obtain about 13.1 g of 1,2-cyclopentyldimethanol (I-1) with a yield of about 86.1%. Example 8

[0032]

[0033] At room temperature, 100 mL of tetrahydrofuran was placed in a 500 mL three-necked flask, and compound VI (10.0 g, 71.4 mmol) was added to form a brown-yellow clear liquid. Then sodium borohydride (2.7 g, 71.4 mmol) was added to generate a large number of bubbles. After the reaction was complete, the reaction solution was filtered and 18% HCl (29.0 g, 142.8 mmol) aqueous solution was slowly added at room temperature at a rate of 10 s / d. After the addition was completed, the solution was a light yellow clear liquid. The temperature was raised to 75 °C for 3 h, and the solution became a brown-yellow clear liquid. The tetrahydrofuran in the reaction solution was dried by rotary evaporation, 100 mL of water and 75 mL of toluene were added, and the mixture was stirred at 50 °C for 20 min until the upper and lower layers were clear. The upper toluene layer was obtained by separation, and the water layer was extracted once with 50 mL toluene, and the toluene layers were combined. Add 75 mL of water to the toluene layer, then add sodium hydroxide (2.0 g, 50.0 mmol), heat to 80 °C and stir for 2 h, remove the toluene layer while hot, separate the water layer and cool to 30 °C, add concentrated hydrochloric acid (7.0 g, 71.4 mmol), adjust the pH to 0.5, heat to 80 °C and stir for 2 h, monitor the reaction by TLC, cool to 50 °C, extract with 50 mL of toluene 3 times, combine the organic phases, dry over anhydrous magnesium sulfate, filter and spin dry to obtain 6.0 g of product with a yield of 67.7%. ESI-MS: m / z 124.0 (147.0 [M+Na] + , 100%). Example 9

[0034]

[0035] Add 50 mL of formic acid to a three-necked flask, add compound A-2 (5.0 g, 40.29 mmol), then add 10% palladium carbon catalyst (0.46 g, 4.29 mmol), stir at room temperature for 24 h, and filter out the catalyst after TLC monitoring of the reaction completion. After vacuum rotary evaporation to remove the solvent, 4.8 g of light yellow oil was obtained. The yield was 91.6%. Structural characterization ESI-MS: m / z 126.0 (149.0 [M+Na]+, 100%) Compound I-2: 1H NMR (400 MHz, CDCl3) δ (ppm): 4.44 (dd, J = 9.4, 7.7 Hz,1H), 3.96 (dd, J = 9.4, 3.2 Hz, 1H), 2.95 (dtd, J = 23.3, 8.8, 3.2 Hz, 2H),2.13 – 1.98 (m, 1H), 1.95 – 1.79 (m, 2H), 1.69 (ddd, J = 11.2, 6.9, 3.2 Hz,1H), 1.62 – 1.45 (m, 2H). Example 10

[0036]

[0037] At room temperature, anhydrous zinc chloride (15.7 g, 11.50 mmol) and sodium borohydride (2.3 g, 5.98 mmol) were added to a 50 mL three-necked flask. After replacing nitrogen three times, 50 mL of anhydrous tetrahydrofuran was slowly injected. The solution turned into a white turbid liquid. After the injection, it was stirred at room temperature for 30 min. The solution turned into a gray-black turbid liquid. Compound I-2 (5.8 g, 46.0 mmol) was then added dropwise at a dropping speed of 1 s / d. Bubbles were generated during the addition. After the addition was completed, the temperature was raised to 60-65 °C and the reaction was continued for 6 h. After the reaction was completed by TLC, the reaction solution was cooled to room temperature, the ice bath was cooled to 0 °C, and 50 mL of water was added for quenching. After the addition was completed, the reaction solution was stirred at room temperature for 3 h, filtered, and the solvent tetrahydrofuran in the reaction solution was dried by spin-drying. The water layer was extracted 3 times with 50 mL of dichloromethane, the organic layers were combined, dried over anhydrous magnesium sulfate for 30 min, and the dichloromethane was dried by spin-drying to obtain 5.0 g of a light yellow oily product with a yield of 83.5%. Structural characterization of compound I-1 ESI-MS: m / z 130.1 (153.1 [M+Na]+, 100%). 1H NMR (400 MHz, CDCl3) δ (ppm): 4.59 – 3.89 (m, 2H), 3.63 (dd, J =11.2, 9.1 Hz, 2H), 3.56 (dd, J = 11.2, 3.8 Hz, 2H), 2.25 (tt, J = 7.7, 4.2Hz, 2H), 1.77 – 1.67 (m, 2H), 1.60 (dtt, J = 11.8, 7.8, 3.6 Hz, 1H), 1.51 –1.40 (m, 1H), 1.17 (dq, J = 13.0, 8.1 Hz, 2H)。

Claims

1. A method for preparing a gliclazide intermediate compound of formula A-1 or formula A-2, characterized in that: Prepared by reduction reaction of compound of formula VI, the reaction equation is: 。 2. The preparation method according to claim 1, characterized in that: The compound of formula A-1 or formula A-2 is further prepared by hydrogenation reaction of the compound of formula I-1 or formula I-2, 。 3. The preparation method according to claim 1, characterized in that: Further preparing the gliclazide intermediate 1,2-cyclopentane dimethanol compound of formula I-1, comprising the steps of preparing a compound of formula A-2 by a reduction reaction of a compound of formula VI, further preparing a compound of formula I-2 by a hydrogenation reaction of the compound of formula A-2, and preparing a compound of formula I-1 by a reduction reaction of the compound of formula I-2, the reaction formula is as follows: 。 4. The preparation method according to claim 1, characterized in that: The preparation of the compound of formula A-1 includes using the compound of formula II as a starting material, and preparing the compound of formula A-1 through depolymerization reaction, [2+2] cycloaddition, ring opening, hydrolysis, and reduction reaction. The reaction formula is as follows: 。 5. The preparation method according to claim 1, characterized in that: The reduction reaction is carried out in the presence of a reducing agent, and the reducing agent used is a boron reducing agent or lithium aluminum hydride.

6. The preparation method according to claim 2, characterized in that: The catalyst used in the hydrogenation reaction is Pd / C or skeleton nickel, and the hydrogen source used is hydrogen gas, formic acid or ammonium formate.

7. The preparation method according to claim 3, characterized in that: The hydrogenation reaction step comprises reacting a compound of formula A-2, formic acid or ammonium formate, and a palladium-carbon catalyst / nickel catalyst to prepare a compound of formula I-2.

8. The preparation method according to claim 6, characterized in that: The hydrogenation reaction solvent is an ether solvent or an ester solvent.

9. The preparation method according to claim 6, characterized in that: The mass ratio of the raw material compound A-1 to the solvent in the hydrogenation reaction is in the range of 1:5-15.

10. A method for preparing gliclazide intermediate 1,2-cyclopentane dimethanol, using the compound of formula II as the starting material, and the reaction formula is as follows: or 。

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