CN107698493A - A kind of preparation method of the piperidones of N Boc 3 - Google Patents

A kind of preparation method of the piperidones of N Boc 3 Download PDF

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Publication number
CN107698493A
CN107698493A CN201711133607.7A CN201711133607A CN107698493A CN 107698493 A CN107698493 A CN 107698493A CN 201711133607 A CN201711133607 A CN 201711133607A CN 107698493 A CN107698493 A CN 107698493A
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piperidones
boc
benzyl
preparation
quaternary ammonium
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帅小华
洪伟
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Shanghai Hobor Chemical Co Ltd
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Shanghai Hobor Chemical Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms

Abstract

The invention discloses a kind of preparation method of the piperidones of N Boc 3, belong to technical field of organic synthesis.The pyridone quaternary ammonium salt of N benzyls 3 carries out reduction reaction with potassium borohydride in the presence of a lewis acid and obtains the piperidones of N benzyls 3；React to obtain the piperidones of N Boc 3 with di-tert-butyl dicarbonate after palladium carbon catalytic hydrogenation conditions again.Compared with existing synthetic method, the pyridone quaternary ammonium salt selective reduction of N benzyls 3 is obtained the piperidones of N benzyls 3 by single step reaction of the present invention, and the reaction has that fast speed, convenient product separation, side reaction is few, the succinct advantage of synthetic route.

Description

A kind of preparation method of N-Boc-3- piperidones
Technical field：
The invention belongs to organic chemistry filed, and in particular to a kind of preparation method of N-Boc-3- piperidones.
Background technology：
N-Boc-3- piperidones is important industrial chemicals, is widely used in pharmaceuticals industry, is the various potent nerves of synthesis The important intermediate of kassinin kinin -1 (NK1) receptor antagonist.It is living that the potent NK1 receptor antagonists show rich potential biology Property, new therapy may be provided for illnesss such as depression, anxiety disorder and vomitings.
At present, the synthetic method of the N-Boc-3- piperidones of document report, mainly there is five kinds：
1) United States Patent (USP) US0053565 is using gamma-butyrolacton as raw material, by benzylamine aminolysis, hydrolysis, esterification and bromoacetic acid Ethyl ester condensation, cyclization, hydrolysis decarboxylation six-step process give birth to 1- benzyl -3- piperidone hydrochlorides, then tertbutyloxycarbonyl on debenzylation N- tertbutyloxycarbonyl -3- piperidones is obtained, course of reaction is as follows：
The method shortcoming is that general line is oversize so that total recovery decline, totle drilling cost rise, the N-Boc-3- piperazines of synthesis Pyridine ketone purity is low, seriously polluted.
2) Chinese patent CN104447511 reacts to obtain uncle N- using 3- pyridones as raw material with di-tert-butyl dicarbonate Butoxy carbonyl -3- hydroxy piperidines, N- tertbutyloxycarbonyl -3- hydroxy piperidines are under tetramethyl piperidine oxides effect, by hypochlorous acid Sodium is oxidized to N- tertbutyloxycarbonyl -3- piperidones, and course of reaction is as follows：
The method does reaction reagent with the substantial amounts of sodium hypobromite aqueous solution, is washed with sodium thiosulfate solution during post processing Wash, cause to produce substantial amounts of waste water, it is very unfriendly to environment.
3) Chinese patent CN103204801 reacts generation quaternary ammonium salt, sodium borohydride using 3- pyridones as raw material with bromobenzyl Tertbutyloxycarbonyl in reduction, palladium carbon debenzylation, through oxalyl chloride, dimethyl sulfoxide (DMSO) low-temperature oxidation obtains N- tertbutyloxycarbonyls -3- Piperidones, course of reaction are as follows：
The method synthesis route is grown, and Swern oxidation reaction conditions are harsh, it is necessary to carried out under -78 DEG C of temperature conditionss, High energy consumption, low yield, be not suitable for industrialized production.
4) Chinese patent CN105949113 is used under the catalysis of platinum carbon first using the hydroxyl hydrochloride of 1- benzyls -3 as raw material Sodium borohydride reduction, activated carbon supported tetrabutyl titanate ester is then added as catalyst, reacts, obtains with di-tert-butyl dicarbonate To 1-Boc-3- hydroxy piperidines, then in the presence of organic base, 1-Boc-3- piperidones is obtained with oxidant reaction, reacts road Line is as follows：
The method makes the cost of whole process route be difficult to decline using noble metal catalyst, plus Swern oxidation reactions Harsh temperature conditions, be not suitable for industrialized production.
5) Chinese patent CN103304472 passes through the reduction of 3- pyridones, piperidine ring nitrogen using 3- pyridones as raw material 1-BOC-3- piperidones is prepared in BOC protections, the three-step approach of Oppenauer oxidations, and reaction scheme is as follows：
Reaction is quenched using sodium hydroxide solution in the method post-processing stages, Al catalysts is generated aluminum hydroxide precipitation, It is not easy to filter, it is difficult to realize amplification production.
In above method, method (1) and (2) environmental pollution are serious；Method (3) to (5) is reaction more than three steps, all There is the oxidation step to 3 hydroxyls of piperidine ring, therefore need a kind of short, environment-friendly, the easy to operate method of step badly at present and use In preparation N-Boc-3- piperidones.
The content of the invention：
It is an object of the invention to for above technical problem, there is provided a kind of synthetic route shortens, reaction reagent material into The preparation method of this low, environment-friendly, concise production process N-Boc-3- piperidones.
A kind of preparation method of N-Boc-3- piperidones, it is technically characterized in that, comprises the following steps：
The first step, N- benzyl -3- pyridones quaternary ammonium salt carry out reduction reaction with potassium borohydride in the presence of a lewis acid Obtain N- benzyl -3- piperidones；
Second step, in the organic solvent containing hydrochloric acid or hydrogen chloride, N- benzyl -3- piperidones is added, palladium carbon catalysis adds After hydrogen, di-tert-butyl dicarbonate is added in the basic conditions and reacts to obtain N-Boc-3- piperidones.
Reaction scheme is as follows：
Further, in the first step, the optional N- benzyls -3- hydroxyls bromination pyrrole of N- benzyl -3- pyridone quaternary ammonium salts Pyridine salt or N- benzyl -3- hydroxy chloride pyridiniujms, i.e. (X) are Cl or Br.
Further, in the first step, the optional zinc chloride of lewis acid, ferric trichloride and alchlor.
Further, in the first step, N- benzyl -3- pyridones quaternary ammonium salt, potassium borohydride and lewis acidic rub You are than being 1：1-3：0.1-0.3, preferably 1：1-1.5：0.1-0.15.
Further, in the first step, investigated using potassium borohydride as reducing agent under Louis acid catalysis N- benzyls- 3- pyridone quaternary ammonium salt selective reductions prepare the reaction of N- benzyl -3- piperidones, by 0.1mol N- benzyl -3- hydroxyl pyrroles Pyridine quaternary ammonium salt and 0.015mol lewis acids are dissolved in 200ml acetonitriles, and 0.15mol potassium borohydrides are slowly added at 0 DEG C, and room temperature is stirred Mix 8 hours, choose different lewis acids, it is as a result as follows：
Sequence number Lewis acid Conversion ratio (%) Selectivity (%)
1 Zinc chloride 100 98.9
2 Ferric trichloride 100 97.6
3 Ferrous chloride 73 86.1
4 Copper bromide 92 11.8
5 Alchlor 100 96.8
6 Nothing 100 0
As a result show, lewis acid：Zinc chloride, ferric trichloride, alchlor, N- benzyl -3- hydroxyls can be significantly improved The selectivity of pyridine quaternary ammonium salt conversion ratio and N- benzyl -3- piperidones.This is probably because lewis acid can activate pyridine ring Structure, be advantageous to the reduction on pyridine ring, so as to improve the conversion ratio of N- benzyl -3- pyridone quaternary ammonium salts；Due to Louis This acid is short of electricity minor structure, can form share electron pair with the lone pair electrons on piperidones carbonylic oxygen atom, make piperidones electric More disperseing for son distribution, so as to be passivated the reducing activity of carbonyl on piperidones, is inhibited on piperidones to a certain extent Carbonyl be then reduced into hydroxyl, so as to improve selectivity.However, ferrous chloride and copper bromide result are poor.
Further, in the second step, organic solvent nail alcohol, ethanol, N- benzyl -3- piperidones and hydrochloric acid or chlorination The mol ratio of hydrogen is 1：1-1.05.
Further, in the second step, palladium carbon dosage is the 5-10% of N- benzyl -3- piperidones weight.
Further, in the second step, the mol ratio of N- benzyl -3- piperidones and di-tert-butyl dicarbonate is 1：1-3, It is preferred that 1：1.5-2.
Further, in the second step, alkalescence condition, which refers to, can add organic bases triethylamine or diisopropyl ethyl amine, Also inorganic bases sodium carbonate or potassium carbonate can be added.
Beneficial effects of the present invention：
(1) compared with existing N-Boc-3- piperidones synthetic method, synthetic route of the present invention is shorter, successfully passes a step The reduction of N- benzyl -3- pyridones quaternary ammonium salt is parked in the stage of ketone by reaction, and chemo-selective obtains piperidinone products, omitted Oxidation step.
(2) reaction condition is more gentle, convenient product separation, side reaction are few, and product is easier to separate and purified.
(3) cost and energy consumption are reduced, reduces environmental pollution, is adapted to industrialized production.
Specific embodiment
Embodiment 1：
The first step, in 2L there-necked flasks, add N- benzyl -3- hydroxyl pyridinium bromide salt 132.6g (0.5mol), zinc chloride 10.2g (0.075mol) and 1L acetonitriles, stirring is opened, potassium borohydride 40.5g (0.75mol) is slowly added under 0 degree, has fed Finish, be stirred at room temperature 8 hours, TLC detection raw material reactions are complete, 100mL saturated ammonium chloride solutions are added dropwise reaction, ethyl acetate is quenched Extract (200Ml*2), organic layer rotary evaporation removes solvent, obtains yellow oil N- benzyl -3- piperidones 85.2g, yield 90%, G/C content 96%, GCMS (m/z):189.11(M).
Second step, above-mentioned product 85.2g (0.45mol) is dissolved in 500mL methanol in 1L there-necked flasks, concentrated hydrochloric acid is added dropwise 45.6g (0.45mol, 36%), 10% palladium carbon 4.3g is added, first lead to nitrogen displacement three times, then be passed through hydrogen, it is small to be stirred at room temperature 3 When, GC detection reactions are complete, filter out palladium-carbon catalyst, 113.8g triethylamines are added in filtrate, after stirring 30 minutes, be added dropwise two Dimethyl dicarbonate butyl ester 147.3g (0.68mol), it is stirred at room temperature 6 hours, GC detection raw materials disappear, and be concentrated under reduced pressure out solvent, residual Thing 600mL ethyl acetate dissolves, then successively with 100mL 0.5mol/L aqueous hydrochloric acid solutions, 100mL saturated sodium bicarbonate solutions Respectively wash once, ethyl acetate layer is concentrated under reduced pressure solvent, adds in normal heptane the stirred crystallization at -5 to 0 DEG C, filtering, obtains slightly yellow Solid N-Boc-3- piperidones 74.0g, yield 82.6%, GC purity:99.0%, mp:36.7-38.2 DEG C,1H NMR (400MHz,CDCl3):δ4.0(2H,br s),3.60-3.57(2H,m),2.49-2.45(2H,m),2.01-1.95(1H,m), 1.46(9H,s).
Embodiment 2：
The first step, in 2L there-necked flasks, add N- benzyl -3- hydroxy chloride pyridiniujm 110.9g (0.5mol), zinc chloride 6.8g (0.05mol) and 1L acetonitriles, stirring is opened, is slowly added to potassium borohydride 32.4 (0.6mol) under 0 degree, charging finishes, room Temperature stirring 9 hours, TLC detection raw material reactions are complete, 100mL saturated ammonium chloride solutions are added dropwise reaction, ethyl acetate extraction is quenched (200Ml*2), organic layer rotary evaporation remove solvent, obtain yellow oil N- benzyl -3- piperidones 83.3g, yield 88%, GC Content 96%, GCMS (m/z):189.11(M).
Second step, above-mentioned product 83.3g (0.44mol) is dissolved in 500mL methanol in 1L there-necked flasks, is passed through hydrogen chloride gas Body 16.9g (0.46mol), 10% palladium carbon 8.3g is added, first leads to nitrogen displacement three times, then be passed through hydrogen, be stirred at room temperature 2 hours, GC detection reactions are complete, filter out palladium-carbon catalyst, 142.2g diisopropyl ethyl amines are added in filtrate, after stirring 30 minutes, Di-tert-butyl dicarbonate 192.1g (0.88mol) is added dropwise, is stirred at room temperature 5 hours, GC detection raw materials disappear, and are concentrated under reduced pressure out molten Agent, residue 600mL ethyl acetate dissolve, then successively with 100mL 0.5mol/L aqueous hydrochloric acid solutions, 100mL unsaturated carbonate hydrogen Sodium solution is respectively washed once, and ethyl acetate layer is concentrated under reduced pressure solvent, is added in normal heptane the stirred crystallization at -5 to 0 DEG C, filtering, is obtained Slightly yellow solid N-Boc-3- piperidones 73.6g, yield 84.0%, GC purity:99.0%, mp:37.1-38.8℃.
Embodiment 3：
The first step, in 2L there-necked flasks, add N- benzyl -3- hydroxy chloride pyridiniujm 110.9g (0.5mol), alchlor 10.0g (0.075mol) and 1L acetonitriles, stirring is opened, potassium borohydride 40.5g (0.75mol) is slowly added under 0 degree, has fed Finish, be stirred at room temperature 8 hours, TLC detection raw material reactions are complete, 100mL saturated ammonium chloride solutions are added dropwise reaction, ethyl acetate is quenched Extract (200Ml*2), organic layer rotary evaporation removes solvent, obtains yellow oil N- benzyl -3- piperidones 84.2g, yield 89%, G/C content 94%.
Second step, above-mentioned product 84.2g (0.45mol) is dissolved in 500mL methanol in 1L there-necked flasks, concentrated hydrochloric acid is added dropwise 47.4g (0.47mol, 36%), 10% palladium carbon 8.4g is added, first lead to nitrogen displacement three times, then be passed through hydrogen, it is small to be stirred at room temperature 2 When, GC detection reactions are complete, filter out palladium-carbon catalyst, 117.9g sodium carbonate is added in filtrate, after stirring 30 minutes, be added dropwise two Dimethyl dicarbonate butyl ester 145.7g (0.67mol), it is stirred at room temperature 7 hours, GC detection raw materials disappear, and be concentrated under reduced pressure out solvent, residual 600mL ethyl acetate and 100mL 0.5mol/L aqueous hydrochloric acid solutions, organic layer 100mL saturated sodium bicarbonate solutions are added in thing Be concentrated under reduced pressure out solvent after washing, add normal heptane at -5 to 0 DEG C stirred crystallization, filtering, obtain slightly yellow solid N-Boc-3- Piperidones 72.1g, yield 81.3%, GC purity:98.6%, mp:36.3-38.3℃.
Embodiment 4：
The first step, in 2L there-necked flasks, add N- benzyl -3- hydroxyl pyridinium bromide salt 132.6g (0.5mol), alchlor 8.0g (0.06mol) and 1L acetonitriles, stirring is opened, is slowly added to potassium borohydride 27.0g (0.5mol) under 0 degree, charging finishes, room Temperature stirring 10 hours, TLC detection raw material reactions are complete, 100mL saturated ammonium chloride solutions are added dropwise reaction, ethyl acetate extraction is quenched (200Ml*2), organic layer rotary evaporation remove solvent, obtain yellow oil N- benzyl -3- piperidones 83.3g, yield 88%, GC Content 94%.
Second step, above-mentioned product 83.3g (0.44mol) is dissolved in 500mL methanol in 1L there-necked flasks, is passed through hydrogen chloride gas Body 16.1g (0.44mol), 10% palladium carbon 4.2g is added, first leads to nitrogen displacement three times, then be passed through hydrogen, be stirred at room temperature 3 hours, GC detection reactions are complete, filter out palladium-carbon catalyst, 151.8g potassium carbonate is added in filtrate, after stirring 30 minutes, two carbon are added dropwise Sour di tert butyl carbonate 144.0g (0.66mol), is stirred at room temperature 8 hours, and GC detection raw materials disappear, and be concentrated under reduced pressure out solvent, residue Middle addition 600mL ethyl acetate and 100mL0.5mol/L aqueous hydrochloric acid solutions, organic layer are washed with 100mL saturated sodium bicarbonate solutions After be concentrated under reduced pressure out solvent, add in normal heptane the stirred crystallization at -5 to 0 DEG C, filtering, obtain slightly yellow solid N-Boc-3- piperazines Pyridine ketone 71.6g, yield 81.7%, GC purity:98.6%, mp:36.5-38.6℃.
Embodiment 5：
The first step, in 2L there-necked flasks, add N- benzyl -3- hydroxyl pyridinium bromide salt 132.6g (0.5mol), ferric trichloride 9.7g (0.06mol) and 1L acetonitriles, stirring is opened, is slowly added to potassium borohydride 32.4g (0.6mol) under 0 degree, charging finishes, room Temperature stirring 9 hours, TLC detection raw material reactions are complete, 100mL saturated ammonium chloride solutions are added dropwise reaction, ethyl acetate extraction is quenched (200Ml*2), organic layer rotary evaporation remove solvent, obtain yellow oil N- benzyl -3- piperidones 84.2g, yield 89%, GC Content 95%.
Second step, above-mentioned product 84.2g (0.45mol) is dissolved in 500mL methanol in 1L there-necked flasks, concentrated hydrochloric acid is added dropwise 47.4g (0.47mol, 36%), 10% palladium carbon 8.4g is added, first lead to nitrogen displacement three times, then be passed through hydrogen, it is small to be stirred at room temperature 2 When, GC detection reactions are complete, filter out palladium-carbon catalyst, add 143.8g diisopropyl ethyl amines in filtrate, stir 30 minutes Afterwards, di-tert-butyl dicarbonate 145.7g (0.67mol) is added dropwise, is stirred at room temperature 5 hours, GC detection raw materials disappear, and are concentrated under reduced pressure out Solvent, 600mL ethyl acetate and 100mL 0.5mol/L aqueous hydrochloric acid solutions, organic layer 100mL saturated carbons are added in residue Sour hydrogen sodium solution is concentrated under reduced pressure out solvent after washing, and adds in normal heptane the stirred crystallization at -5 to 0 DEG C, filtering, obtains slightly yellow solid Body N-Boc-3- piperidones 74.7g, yield 84.2%, GC purity:98.8%, m p:36.3-38.2℃.
Embodiment 6：
The first step, in 2L there-necked flasks, add N- benzyl -3- hydroxy chloride pyridiniujm 110.9g (0.5mol), ferric trichloride 12.2g (0.075mol) and 1L acetonitriles, stirring is opened, potassium borohydride 40.5g (0.75mol) is slowly added under 0 degree, has fed Finish, be stirred at room temperature 8 hours, TLC detection raw material reactions are complete, 100mL saturated ammonium chloride solutions are added dropwise reaction, ethyl acetate is quenched Extract (200Ml*2), organic layer rotary evaporation removes solvent, obtains yellow oil N- benzyl -3- piperidones 85.1g, yield 90%, G/C content 95%.
Second step, above-mentioned product 85.1g (0.45mol) is dissolved in 500mL methanol in 1L there-necked flasks, concentrated hydrochloric acid is added dropwise 47.9g (0.47mol, 36%), 10% palladium carbon 4.3g is added, first lead to nitrogen displacement three times, then be passed through hydrogen, it is small to be stirred at room temperature 3 When, GC detection reactions are complete, filter out palladium-carbon catalyst, 155.2g potassium carbonate is added in filtrate, after stirring 30 minutes, be added dropwise two Dimethyl dicarbonate butyl ester 196.4g (0.9mol), it is stirred at room temperature 8 hours, GC detection raw materials disappear, and be concentrated under reduced pressure out solvent, residue Middle addition 600mL ethyl acetate and 100mL 0.5mol/L aqueous hydrochloric acid solutions, organic layer are washed with 100mL saturated sodium bicarbonate solutions After be concentrated under reduced pressure out solvent, add in normal heptane the stirred crystallization at -5 to 0 DEG C, filtering, obtain slightly yellow solid N-Boc-3- piperazines Pyridine ketone 73.2g, yield 81.6%, GC purity:98.7%, mp:36.4-38.5℃.
The general principle and principal character and advantages of the present invention of the present invention has been shown and described above.The technology of the industry Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the simply explanation described in above-described embodiment and specification is originally The principle of invention, without departing from the spirit and scope of the present invention, various changes and modifications of the present invention are possible, these changes Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its Equivalent thereof.

Claims (8)

1. a kind of preparation method of N-Boc-3- piperidones, it is characterised in that comprise the following steps：
The first step, N- benzyl -3- pyridones quaternary ammonium salt carry out reduction reaction with potassium borohydride in the presence of a lewis acid and obtained N- benzyl -3- piperidones；
Second step, in the organic solvent containing hydrochloric acid or hydrogen chloride, N- benzyl -3- piperidones is added, after palladium carbon catalytic hydrogenation, Di-tert-butyl dicarbonate is added in the basic conditions to react to obtain N-Boc-3- piperidones.
A kind of 2. preparation method of N-Boc-3- piperidones according to claim 1, it is characterised in that：The first step In, N- benzyl -3- pyridones quaternary ammonium salt is selected from N- benzyl -3- hydroxyl pyridinium bromide salt or N- benzyl -3- hydroxy chloride pyridines Salt.
A kind of 3. preparation method of N-Boc-3- piperidones according to claim 1, it is characterised in that：The first step In, lewis acid is selected from zinc chloride, ferric trichloride or alchlor.
A kind of 4. preparation method of N-Boc-3- piperidones according to claim 1, it is characterised in that：The first step In, N- benzyl -3- pyridones quaternary ammonium salt, potassium borohydride and lewis acidic mol ratio are 1：1-1.5：0.1-0.15.
A kind of 5. preparation method of N-Boc-3- piperidones according to claim 1, it is characterised in that：The second step In, organic solvent is selected from methanol or ethanol, and N- benzyl -3- piperidones is 1 with the mol ratio of hydrochloric acid or hydrogen chloride：1-1.05.
A kind of 6. preparation method of N-Boc-3- piperidones according to claim 1, it is characterised in that：The second step In, palladium carbon dosage is the 5-10% of N- benzyl -3- piperidones weight.
A kind of 7. preparation method of N-Boc-3- piperidones according to claim 1, it is characterised in that：The second step In, the mol ratio of N- benzyl -3- piperidones and di-tert-butyl dicarbonate is 1：1.5-2.
A kind of 8. preparation method of N-Boc-3- piperidones according to claim 1, it is characterised in that：The second step In, alkalescence condition, which refers to, adds organic base or inorganic base；Organic base is selected from triethylamine or diisopropyl ethyl amine, and inorganic base is selected from carbon Sour sodium or potassium carbonate.
CN201711133607.7A 2017-11-15 2017-11-15 A kind of preparation method of the piperidones of N Boc 3 Pending CN107698493A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6984651B2 (en) * 2000-06-21 2006-01-10 Bristol-Myers Squibb Pharma, Company Piperidine amides as modulators of chemokine receptor activity
CN104529872A (en) * 2014-12-10 2015-04-22 天津孚音生物科技发展有限公司 Synthetic method for benidipine hydrochloride intermediate
CN104822657A (en) * 2012-08-15 2015-08-05 默沙东公司 3-aminocycloalkyl compounds as RORgammat inhibitors and uses thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6984651B2 (en) * 2000-06-21 2006-01-10 Bristol-Myers Squibb Pharma, Company Piperidine amides as modulators of chemokine receptor activity
CN104822657A (en) * 2012-08-15 2015-08-05 默沙东公司 3-aminocycloalkyl compounds as RORgammat inhibitors and uses thereof
CN104529872A (en) * 2014-12-10 2015-04-22 天津孚音生物科技发展有限公司 Synthetic method for benidipine hydrochloride intermediate

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
K. RAJESH, ET AL: "Ultrasound-promoted synthesis of novel bipodal and tripodalpiperidin-4-ones and silica chloride mediated conversion to its piperidin-4-ols: Synthesis and structural confinements", 《ULTRASONICS SONOCHEMISTRY》 *
刘翊纶: "《碱金属-无机化学丛书》", 31 October 1998 *

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Application publication date: 20180216