Synthetic method of medical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine

Abstract

The invention provides a synthesis method of a medical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine, which comprises the following steps: step S1, trans-4-hydroxy-D-proline methyl ester hydrochloride is used as a raw material, under the action of triethylamine, a reaction is carried out for 2-4 hours, and the reaction product is subjected to post-treatment to obtain the (3R, 5R)-3-Boc-amino-5-fluoropiperidine. Dichloromethane is used as a solvent to react with triphenylchloromethane to obtain (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester; s2, the (4S)-4-hydroxy-1-(triphenyl methyl)-D-proline methyl ester is subjected to oxidation, and 4-oxy-1-(triphenyl methyl)-D-proline methyl ester is obtained; s3, enabling the compound 4-oxo-1-(triphenyl methyl)-D-proline methyl ester to react with hydroxylamine hydrochloride, so as to obtain a compound hydroxylamino-1-(triphenyl methyl)-D-proline methyl ester; step S9, the compound (3R, 5R)-3-Boc amino-1-triphenyl-5-fluoropiperidine is subjected to Trt removal under the action of hydrochloric acid, and a compound (3R, 5R)-3-Boc amino-5-fluoropiperidine is obtained; according to the method disclosed by the invention, the (3R, 5R)-3-Boc amino-5-fluoropiperidine can be efficiently and economically synthesized by optimizing a reaction route.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical intermediate synthesis, in particular to a method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine. Background Art

[0002] (3R,5R)-3-Bocamino-5-fluoropiperidine is an important pharmaceutical intermediate used to synthesize a variety of biologically active drug molecules. Existing synthesis methods suffer from complex procedures, low yields, and high costs. Summary of the Invention

[0003] In view of this, the object of the present invention is to provide a method for synthesizing the pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine efficiently and economically by optimizing the reaction route.

[0004] The present invention is achieved by the following method: a method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine, the method comprising the following steps:

[0005] Step S1, using trans-4-hydroxy-D-proline methyl ester hydrochloride as a raw material, reacting with triphenylmethane in the presence of triethylamine and dichloromethane as a solvent to obtain (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester;

[0006] Step S2, (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester is oxidized to obtain 4-oxo-1-(triphenylmethyl)-D-proline methyl ester;

[0007] Step S3, reacting the compound 4-oxo-1-(triphenylmethyl)-D-proline methyl ester with hydroxylamine hydrochloride to obtain the compound hydroxylamino-1-(triphenylmethyl)-D-proline methyl ester;

[0008] Step S4, reducing the compound hydroxyamino-1-(triphenylmethyl)-D-proline methyl ester to obtain 4-amino-1-(triphenylmethyl)-D-proline methyl ester;

[0009] Step S5, the compound 4-amino-1-(triphenylmethyl)-D-proline methyl ester is resolved to obtain (2S,4R)-4-amino-1-(triphenylmethyl)-proline methyl ester;

[0010] Step S6, reacting the compound (2S,4R)-4-amino-1-(triphenylmethyl)-proline methyl ester with Boc2O in the presence of triethylamine to obtain (2S,4R)-4-Bocamino-1-(triphenylmethyl)-proline methyl ester;

[0011] Step S7, compound (2S,4R)-4-Boc amino-1-(triphenylmethyl)-proline methyl ester is reduced by lithium aluminum hydride to obtain tert-butyl ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamate;

[0012] Step S8, compound tert-butyl ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamate is reacted with diethylaminosulfur trifluoride (DAST) reagent to obtain (3R,5R)-3-Boc amino-1-triphenyl-5-fluoropiperidine;

[0013] Step S9, compound (3R,5R)-3-Boc amino-1-triphenyl-5-fluoropiperidine is deprotected Trt under the action of hydrochloric acid to obtain compound (3R,5R)-3-Boc amino-5-fluoropiperidine.

[0014] Further, in step S1, trans-4-hydroxy-D-proline methyl ester hydrochloride is used as a raw material, and reacts with triphenylmethyl chloride to obtain (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester, and triethylamine is used as a solvent, and dichloromethane is used as a solvent.

[0015] Further, in step S2, (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester (1) is oxidized to obtain 4-oxo-1-(triphenylmethyl)-D-proline methyl ester, and toluene or dichloromethane is used as a solvent.

[0016] Further, in step S3, compound 4-oxo-1-(triphenylmethyl)-D-proline methyl ester reacts with hydroxylamine hydrochloride to obtain compound 4-hydroxylamino-1-(triphenylmethyl)-D-proline methyl ester; and ethanol is used as a solvent.

[0017] Further, in step S4, compound 4-hydroxylamino-1-(triphenylmethyl)-D-proline methyl ester is reduced to obtain 4-amino-1-(triphenylmethyl)-D-proline methyl ester; and ethanol is used as a solvent.

[0018] Further, in step S5, compound 4-amino-1-(triphenylmethyl)-D-proline methyl ester is resolved to obtain (2S,4R)-4-amino-1-(triphenylmethyl)-proline methyl ester; and ethanol is used as a solvent.

[0019] Further, in step S6, compound (2S,4R)-4-amino-1-(triphenylmethyl)-proline methyl ester reacts with Boc anhydride to obtain (2S,4R)-4-Boc amino-1-(triphenylmethyl)-proline methyl ester; and dichloromethane is used as a solvent.

[0020] Furthermore, in step S7, the compound (2S,4R)-4-Bocamino-1-(triphenylmethyl)-proline methyl ester is reduced with lithium aluminum hydride to obtain tert-butyl ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamate; the solvent used is tetrahydrofuran.

[0021] Furthermore, in step S8, the compound ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamic acid tert-butyl ester reacts with diethylaminosulfur trifluoride (DAST) reagent to obtain (3R,5R)-3-Bocamino-1-triphenyl-5-fluoropiperidine; the solvent used is tetrahydrofuran.

[0022] Furthermore, in step S9, (3R,5R)-3-Bocamino-1-triphenyl-5-fluoropiperidine (8) is reacted with hydrochloric acid to obtain compound (3R,5R)-3-Bocamino-5-fluoropiperidine (9); the solvent used is ethanol.

[0023] The beneficial effects of the present invention are as follows: the present invention provides a method for synthesizing (3R,5R)-3-Bocamino-5-fluoropiperidine, the synthetic route is simple, the process selection is reasonable, the raw materials are simple and easily available, and the operation and post-processing are convenient; the synthetic route is efficient and economical, the total yield can reach more than 30%, and the operation is simple, which is suitable for industrial scale-up production. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is a structural schematic diagram of the present invention. DETAILED DESCRIPTION

[0025] The present invention will be further described below with reference to the accompanying drawings.

[0026] See also Figure 1 As shown, the present invention provides: (3R, 5R)-3-Bocamino-5-fluoropiperidine, the chemical structure of which is as follows:

[0027]

[0028] The application discloses a synthesis method of (3R, 5R)-3-Boc-amino-5-fluoropiperidine, which comprises the following steps: taking trans 4-hydroxy-D-proline methyl ester hydrochloride as raw material, and reacting with triphenylmethyl chloride to obtain (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester (1); the (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester (1) is subjected to oxidation to obtain 4-oxo-1-(triphenylmethyl)-D-proline methyl ester (2); the compound (2) is reacted with hydroxylamine hydrochloride to obtain compound 4-hydroxylamino-1-(triphenylmethyl)-D-proline methyl ester (3); the compound (3) is subjected to reduction to obtain 4-amino-1-(triphenylmethyl)-D-proline methyl ester (4); the compound (4) is subjected to separation to obtain (2S, 4R)-4-amino-1-(triphenylmethyl)-proline methyl ester (5); the compound (5) is reacted with Bocce acid anhydride to obtain (2S, 4R)-4-Boc amino-1-(triphenylmethyl)-proline methyl ester (6); the compound (2S, 4R)-4-Boc amino-1-(triphenylmethyl)-proline methyl ester (6) is subjected to reduction by lithium aluminum hydride to obtain ((3R, 5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl) tert-butyl carbamate (7); the compound ((3R, 5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl) tert-butyl carbamate (7) is reacted with diethylamino sulfur trifluoride (DAST) reagent to obtain (3R, 5R)-3-Boc amino-1-triphenyl-5-fluoropiperidine (8); and the (3R, 5R)-3-Boc amino-1-triphenyl-5-fluoropiperidine (8) is subjected to the action of hydrochloric acid to obtain compound (3R, 5R)-3-Boc amino-5-fluoropiperidine (9).

[0029] The synthesis route is as follows:

[0030]

[0031] The first step is synthesis of (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester (1)

[0032] Trans 4-hydroxy-D-proline methyl ester hydrochloride (500g, 2.75mmol) and dichloromethane (5000g) are added into a reaction bottle, triethylamine (696g, 6.88mmol, 2.5eq) is added dropwise under temperature control of 20-30 DEG C, after the addition of triethylamine is completed, triphenylmethyl chloride (767g, 2.75mmol, 1.0eq) is added in batches under temperature control of 20-30 DEG C, reaction is carried out for 2h under temperature control of 20-30 DEG C after the addition is completed, and the reaction is stopped when the content of triphenylmethyl chloride in LC is less than 2%.

[0033] Water (2500 g) was added to the reaction solution and stirred for 10 min. The mixture was allowed to stand for separation. The organic phase was concentrated under reduced pressure to give (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester (1070 g, 2.76 mmol) with a yield of 100.00%.

[0034] Step 2: Synthesis of 4-oxo-1-(triphenylmethyl)-D-proline methyl ester (2)

[0035] Compound (1) (1.06 kg, 2.75 mmol), dichloromethane (10.6 kg), and 2,2,6,6-tetramethylpiperidinoxide (21.4 g, 0.14 mmol) were added to a reaction kettle. The temperature was lowered to 0-10°C and trichloroisocyanuric acid (763 g, 3.28 mmol) was added in batches. After the addition, the temperature was kept at 0-10°C for 2 h. The reaction was stopped by controlling the concentration of compound (1) to less than 1% by LC.

[0036] The temperature was controlled at 0-10°C, 20% aqueous potassium carbonate solution (5.3 kg) was added, and stirred for 10 min. The mixture was allowed to stand for separation. The aqueous phase was extracted once with DCM (2.12 kg). The combined DCM phases were concentrated under pressure to give 4-oxo-1-(triphenylmethyl)-D-proline methyl ester (1005 g, 2.62 mmol) in a yield of 95.26%.

[0037] Step 3: Synthesis of 4-hydroxyamino-1-(triphenylmethyl)-D-proline methyl ester (3)

[0038] Compound (2) (1000 g, 2.59 mmol), ethanol (5000 g), and triethylamine (525 g, 5.19 mmol) were added to a reaction kettle. Hydroxylamine hydrochloride (270 g, 3.89 mmol) was added at 20-30°C. After the addition, the temperature was raised to reflux and the reaction was reacted for 12 h. The concentration of compound (2) was controlled to be below 1% by LC, and the reaction was stopped.

[0039] The reaction solution was cooled, and water (10 kg) was slowly added dropwise at 20-30 ° C., stirred and crystallized. The temperature was cooled to 10 ° C., stirred for 1 h, and then filtered. The solid was washed with water twice (500 g × 2). The solid was dried under reduced pressure at 40-50 ° C to obtain 4-hydroxyamino-1-(triphenylmethyl)-D-proline methyl ester (904 g, 2.26 mmol) with a yield of 87.01%.

[0040] Step 4: Synthesis of 4-amino-1-(triphenylmethyl)-D-proline methyl ester (4)

[0041] Compound (3) (904 g, 2.26 mmol), ethanol (4520 g), and Raney nickel (180 g) were added to an autoclave, hydrogen was 1.0-2.0 MPa, and the temperature was 60-70°C. The reaction was continued for 15 h. The reaction was stopped when the concentration of compound (3) was below 2% by LC.

[0042] Cool to 20 ℃ nitrogen pressure filter, the filtrate was concentrated to give 4-amino-1- (triphenylmethyl) -D-proline methyl ester (873 g, 2.26 mmol), the yield was 100.00%.

[0043] Step 5: Synthesis of (2S, 4R) -4-amino-1- (triphenylmethyl) -proline methyl ester (5)

[0044] Compound (4) (873 g, 2.26 mmol), ethanol (6111 g) was added to the reaction kettle, temperature control 20-30 ℃, R-mandelic acid (240 g, 1.58 mmol) was added, and after the addition was completed, the temperature was controlled at 20-30 ℃, and the crystal was stirred. After 3 h, the temperature was lowered to 0 ℃ and filtered. The solid was dried at 40-50 ℃ after heating to reflux and dissolving in ethanol (6111 g). After stirring at 0 ℃ for 1 h, the filtrate was obtained. The mandelic acid salt of compound (4) (380 g) was obtained.

[0045] Compound (4) (380 g), water (1140 g) was added to the reaction bottle, and 30% sodium hydroxide aqueous solution (100 g) was added at 20-30 ℃. Dichloromethane was extracted twice (1140 g x 2), and the dichloromethane phase was concentrated under reduced pressure to give (2S, 4R) -4-amino-1- (triphenylmethyl) -proline methyl ester (270 g, 0.70 mmol), the yield was 30.93%.

[0046] Step 6: Synthesis of (2S, 4R) -4-Boc amino-1- (triphenylmethyl) -proline methyl ester (6)

[0047] Compound (5) (270 g, 0.70 mmol), dichloromethane (2700 g) was added to the reaction bottle, and triethylamine (106 g, 1.05 mmol, 1.5 eq) was added dropwise at 20-30 ℃. After the addition of triethylamine was completed, Boc2O (168 g, 0.77 mmol, 1.1 eq) was added in batches at 20-30 ℃. After the addition was completed, the reaction was carried out at 20-30 ℃ for 2 h. The content of compound (5) was less than 1% in LC, and the reaction was stopped.

[0048] Water (2500 g) was added to the reaction solution and stirred for 10 min, then separated, and (2S, 4R) -4-Boc amino-1- (triphenylmethyl) -proline methyl ester (341 g, 0.70 mmol) was obtained by concentrating under reduced pressure, the yield was 100.00%.

[0049] Step 7: Synthesis of ((3R, 5S) -5- (hydroxymethyl) -1-triphenylpyrrolidin-3-yl) carbamic acid tert-butyl ester (7)

[0050] Compound (6) (340 g, 0.70 mmol) and tetrahydrofuran (3400 g) were added to the reaction flask, and the temperature was lowered to 0-10°C and lithium aluminum tetrahydride (53 g, 1.4 mmol) was added in batches. After the addition, the temperature was kept at 0-10°C and the reaction was continued for 2 h. The concentration of compound (6) in LC was controlled to be below 1.5%, and the reaction was stopped.

[0051] Sodium sulfate decahydrate (680 g) was slowly added while controlling the temperature at 0-10°C, and the mixture was stirred for 1 h and then filtered. The filtrate was concentrated under reduced pressure to give tert-butyl ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamate (300 g, 0.65 mmol) in a yield of 93.63%.

[0052] Step 8: Synthesis of (3R,5R)-3-Bocamino-1-triphenyl-5-fluoropiperidine (8)

[0053] Compound (7) (300 g, 0.65 mmol) and tetrahydrofuran (2400 g) were added to the reaction flask, and diethylaminosulfur trifluoride (DAST) reagent (210 g, 1.3 mmol) was added dropwise at a temperature of 0-15°C. After the addition, the temperature was kept at 10-15°C and the reaction was continued for 12 h. The concentration of compound (7) in LC was controlled to be below 1.0%, and the reaction was stopped.

[0054] The temperature was lowered to 10-20° C., and 6% sodium carbonate solution (3000 g) was slowly added to quench the reaction. The mixture was extracted twice with ethyl acetate (1200 g×2). The organic phases were combined, washed once with water, and dried to give a light yellow crude product.

[0055] Column chromatography: The crude product was added with silica gel and eluent (P:E=100:1 to P:E=10:1) to elute the product. The eluate was spin-dried to give (3R,5R)-3-Bocamino-1-triphenyl-5-fluoropiperidine (188 g, 0.41 mmol) in a yield of 62.46%.

[0056] Step 9: Synthesis of (3R,5R)-3-Bocamino-5-fluoropiperidine (9)

[0057] Compound (8) (188 g, 0.41 mmol) and ethanol (940 g) were added to a reaction flask, and 6% hydrochloric acid (497 g, 0.82 mmol) was added at 10-20°C. After the addition, the mixture was reacted at 10-20°C for 3 h. The concentration of compound (8) was controlled to be below 1.0% by LC, and the reaction was stopped.

[0058] The reaction mixture was cooled to 5°C and filtered. The filter cake was rinsed with a small amount of ethanol and discarded. The filtrate was decompressed to remove ethanol. The residue was adjusted to pH 3-4 with 10% aqueous citric acid solution and extracted twice with ethyl acetate (576 g x 2). The organic phase was discarded, and the aqueous phase was adjusted to pH 8-9 with saturated sodium carbonate and extracted four times with dichloromethane (940 g x 4). The organic phases were combined, washed once with water, and concentrated under reduced pressure to obtain the compound (3R,5R)-3-Bocamino-5-fluoropiperidine (75 g, 0.34 mmol) in a yield of 84.18%.

[0059] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made according to the scope of the patent application of the present invention should fall within the scope of the present invention.

Claims

1. A method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine, characterized in that: The method comprises the following steps: Step S1, using trans-4-hydroxy-D-proline methyl ester hydrochloride as a raw material, reacting with triphenylmethane in the presence of triethylamine and dichloromethane as a solvent to obtain (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester; Step S2, (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester is oxidized to obtain 4-oxo-1-(triphenylmethyl)-D-proline methyl ester; Step S3, reacting the compound 4-oxo-1-(triphenylmethyl)-D-proline methyl ester with hydroxylamine hydrochloride to obtain the compound hydroxylamino-1-(triphenylmethyl)-D-proline methyl ester; Step S4, reducing the compound hydroxyamino-1-(triphenylmethyl)-D-proline methyl ester to obtain 4-amino-1-(triphenylmethyl)-D-proline methyl ester; Step S5, the compound 4-amino-1-(triphenylmethyl)-D-proline methyl ester is resolved to obtain (2S,4R)-4-amino-1-(triphenylmethyl)-proline methyl ester; Step S6, reacting the compound (2S,4R)-4-amino-1-(triphenylmethyl)-proline methyl ester with Boc2O in the presence of triethylamine to obtain (2S,4R)-4-Bocamino-1-(triphenylmethyl)-proline methyl ester; Step S7, reducing the compound (2S,4R)-4-Bocamino-1-(triphenylmethyl)-proline methyl ester with lithium aluminum tetrahydride to obtain tert-butyl ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamate; Step S8, reacting the compound tert-butyl ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamate with diethylaminosulfur trifluoride (DAST) reagent to obtain (3R,5R)-3-Bocamino-1-triphenyl-5-fluoropiperidine; Step S9: De-Trt the compound (3R,5R)-3-Bocamino-1-triphenyl-5-fluoropiperidine under the action of hydrochloric acid to obtain the compound (3R,5R)-3-Bocamino-5-fluoropiperidine.

2. A method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S1, trans-4-hydroxy-D-proline methyl ester hydrochloride is used as a raw material to react with triphenylmethane to obtain (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester under the action of triethylamine, and the solvent used is dichloromethane.

3. A method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S2, (4S)-4-hydroxy-1-(triphenylmethyl)-D-proline methyl ester (1) is oxidized to obtain 4-oxo-1-(triphenylmethyl)-D-proline methyl ester, and the solvent used is toluene or dichloromethane.

4. The method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S3, the compound 4-oxo-1-(triphenylmethyl)-D-proline methyl ester reacts with hydroxylamine hydrochloride to obtain the compound 4-hydroxyamino-1-(triphenylmethyl)-D-proline methyl ester; the reagent used is ethanol.

5. The method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S4, the compound 4-hydroxyamino-1-(triphenylmethyl)-D-proline methyl ester is reduced to obtain 4-amino-1-(triphenylmethyl)-D-proline methyl ester; the solvent used is ethanol.

6. The method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S5, the compound 4-amino-1-(triphenylmethyl)-D-proline methyl ester is split to obtain (2S,4R)-4-amino-1-(triphenylmethyl)-proline methyl ester; the solvent used is ethanol.

7. The method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S6, the compound (2S,4R)-4-amino-1-(triphenylmethyl)-proline methyl ester reacts with Boc anhydride to obtain (2S,4R)-4-Bocamino-1-(triphenylmethyl)-proline methyl ester; the solvent used is dichloromethane.

8. The method for synthesizing a pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S7, the compound (2S,4R)-4-Bocamino-1-(triphenylmethyl)-proline methyl ester is reduced with lithium aluminum hydride to obtain tert-butyl ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamate; the solvent used is tetrahydrofuran.

9. The method for synthesizing the pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S8, the compound ((3R,5S)-5-(hydroxymethyl)-1-triphenylpyrrolidin-3-yl)carbamic acid tert-butyl ester reacts with diethylaminosulfur trifluoride (DAST) reagent to obtain (3R,5R)-3-Bocamino-1-triphenyl-5-fluoropiperidine; the solvent used is tetrahydrofuran.

10. The method for synthesizing the pharmaceutical intermediate (3R, 5R)-3-Boc-amino-5-fluoropiperidine according to claim 1, characterized in that: In step S9, (3R,5R)-3-Bocamino-1-triphenyl-5-fluoropiperidine (8) is reacted with hydrochloric acid to obtain compound (3R,5R)-3-Bocamino-5-fluoropiperidine (9); the solvent used is ethanol.

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