[ CAS No. 64051-79-2 ] {[proInfo.proName]}

Name: 64051-79-2|3-Hydroxypiperidine Hydrochloride|98%
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SKU: A242744
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Quality Control of [ 64051-79-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 64051-79-2 ]

CAS No. :	64051-79-2	MDL No. :	MFCD00012772
Formula :	C₅H₁₂ClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VLECDMDGMKPUSK-UHFFFAOYSA-N
M.W :	137.61	Pubchem ID :	2723962
Synonyms :

Calculated chemistry of [ 64051-79-2 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	38.88
TPSA :	32.26 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.81 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.47
Log Po/w (WLOGP) :	0.15
Log Po/w (MLOGP) :	0.21
Log Po/w (SILICOS-IT) :	0.73
Consensus Log Po/w :	0.31

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.99
Solubility :	14.1 mg/ml ; 0.103 mol/l
Class :	Very soluble
Log S (Ali) :	-0.72
Solubility :	26.4 mg/ml ; 0.192 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.44
Solubility :	50.3 mg/ml ; 0.366 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.56

Safety of [ 64051-79-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 64051-79-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 64051-79-2 ]
Downstream synthetic route of [ 64051-79-2 ]

[ 64051-79-2 ] Synthesis Path-Upstream 1~5

1
[ 64051-79-2 ]
[ 100-44-7 ]
[ 14813-01-5 ]

Yield	Reaction Conditions	Operation in experiment
56.9%	With triethylamine In toluene	REFERENCE EXAMPLE 4 A mixture of 15.0 g of 3-hydroxypiperidine hydrochloride, 13.8 g of benzyl chloride, 22.1 g of triethylamine and 120 ml of toluene was stirred at reflux for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated and distilled under reduced pressure to obtain 11.8 g of 1-benzyl-3-hydroxypiperidine (yield: 56.9percent). b.p.: 125°-126° C./3.5 mmHg NMR spectrum (CCl₄, δ): 1.30-1.90(4H, broad), 2.20-2.50(4H, broad), 3.45(2H, s), 3.40-3.90(1H, broad), 7.20(5H, s)

Reference： [1] Patent: US4448964, 1984, A,

2
[ 24424-99-5 ]
[ 64051-79-2 ]
[ 85275-45-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine In dichloromethane at 20℃; for 2 h;	Preparation Example 1 : Synthesis of 2,4-bis-trifluoromethyl-5,6.,7.8- tetrahydropyrido [3 ,4-d]pyrimidine hydrochloride(O Synthesis of S-hydroxy-piperidine-l-carboxylic acid t-butyl ester1.0 equivalent of dibutyl dicarbonate (159 g) in 200 mL of methylene chloride were slowly added to a mixture of 3 -hydroxy piperidine hydrochloride (100 g, 0.73 mol) and 1.1 equivalents of triethylamine (111 mL) in methylene chloride(800 mL) at room temperature. Then, the resulting mixture was stirred additionally for 2 hours. After the reaction was complete, the reaction solution was washed with a 1.0 N hydrochloric acid aqueous solution (1.0 L) and the organic layer was concentrated to give 138 g (yield: 94percent) of the title compound as a white solid. <n="38"/>¹R NMR(500 MHz, CDCl₃) δl.35-1.55 (HH, m), 1.75 (IH, m), 1.88 (IH, m), 3.08 (2H, m), 3.53(1H, m), 3.73 (2H, br d, J=5.6 Hz).
88%	With triethylamine In dichloromethane	Preparation 117: 1,1-dimethylethyl 3-hydroxypiperidine-l-carboxylate To a solution of piperidin-3-ol hydrochloride salt (10.1 g, 0.1 MMOL) in dichloromethane (30 ML) and triethylamine (13.3 ml, 95.4 MMOL) was added a solution of di-tert-butyl dicarbonate (19.8 g, 90.9 MMOL) dropwise in dichloromethane. Upon completion the reaction mixture was added to diethyl ether (120 ml) washed with hydrochloric acid (1 M) and then with brine. The combined organic extracts were dried (MGS04) and concentrated in vacuo to give the title compound as a light yellow oil (17.7 g, 88percent).

Reference： [1] Patent: WO2009/82134, 2009, A2, . Location in patent: Page/Page column 36-37
[2] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 7, p. 1645 - 1649
[3] Patent: WO2004/72086, 2004, A2, . Location in patent: Page 179
[4] Organic letters, 2000, vol. 2, # 2, p. 155 - 158
[5] Journal of Medicinal Chemistry, 2008, vol. 51, # 15, p. 4601 - 4608
[6] Patent: EP1557418, 2005, A1, . Location in patent: Page/Page column 192-193

3
[ 34619-03-9 ]
[ 64051-79-2 ]
[ 85275-45-2 ]

Reference： [1] Patent: US2001/44454, 2001, A1,

4
[ 64051-79-2 ]
[ 501-53-1 ]
[ 95798-22-4 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium carbonate In tetrahydrofuran; water at 20℃; for 5 h;	To a solution 5-A (10.00 g, 73 mmol) in THF/H₂0 (50 mL/50 ml_), was added Na₂C0₃ (23.10 g, 218 mmol). CbzCI (14.90 g, 87 mmol) was added dropwise and the reaction stirred at rt for 5h. The mixture was extracted with EtOAc (100 mL x 3) and the combined the organic layers washed with brine, dried ( gS0₄), filtered and concentrated. The residue obtained was purified by silica gel column chromatography with EtOAc/Pet ether=1/100~1/4 to give 5-B (16.50 g 96 percent) as a colorless oil. TLC: Rf=0.65 silica gel EtOAc/Pet ether=1/1 v/v
95%	With triethylamine In dichloromethane at 0℃; for 19 h;	10 Step 4: preparation of 3-Hydroxy-piperidine-1-carboxylic acid benzyl ester. Tosuspension of piperidin-3-ol hydrochloride (134 g, 0.974 mol) and triethylamine (276 mL, 1.98 mol) in dichloromethane (2 L) at 0 °C was added a solution of benzyl chloroformate (140 mL, 0.981 mol) in dichloromethane (100 mL) drop wise over 2.5 h. The reaction was allowed to stir for an additional 30 mm at 0 °C, then allowed to warm15 to ambient temperature over 16 h, after which it was quenched with 1 N hydrochloric acid (3 L) and allowed to stir for 30 mm. The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo to afford the title compound (218 g, 95 percent).1H-NMR (CDCI3) 67.29-7.41 (m, 5H), 5.14 (s, 2H), 3.59-3.85 (m, 3H), 3.13-3.27 (m, 2H), 2.18 (bs, 1H), 1.74-1.94 (m, 2H), 1.38-1.61 (m, 2H).

Reference： [1] Patent: WO2014/32, 2014, A1, . Location in patent: Page/Page column 44; 45
[2] Patent: WO2014/68527, 2014, A1, . Location in patent: Page/Page column 75; 15

5
[ 64051-79-2 ]
[ 1885-14-9 ]
[ 95798-22-4 ]

Reference： [1] Patent: US5753659, 1998, A,

[ 64051-79-2 ] Synthesis Path-Downstream 1~39

1
[ 19260-33-4 ]
[ 64051-79-2 ]
[ 121138-45-2 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1988,vol. 38,p. 1666 - 1670

2
[ 541-41-3 ]
[ 64051-79-2 ]
[ 73193-61-0 ]

Reference： [1]Tetrahedron Letters,1993,vol. 34,p. 3863 - 3866

3
[ 88712-56-5 ]
[ 64051-79-2 ]
methyl 3-piperidinyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate hydrochloride [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1988,vol. 38,p. 1666 - 1670

4
[ 64051-79-2 ]
5-Chlorocarbonyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 2-cyano-ethyl ester [ No CAS ]
[ 121138-39-4 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1988,vol. 38,p. 1666 - 1670

5
[ 64051-79-2 ]
[ 4055-39-4 ]
[ 84397-50-2 ]

Reference： [1]Journal of Medicinal Chemistry,1983,vol. 26,p. 1453 - 1457

6
[ 64051-79-2 ]
[ 407-25-0 ]
[ 73193-62-1 ]

Reference： [1]Journal of Organic Chemistry,1980,vol. 45,p. 2307 - 2315

7
[ 64051-79-2 ]
[ 57303-04-5 ]
(5Z,8Z,11Z,14Z)-1-(3-Hydroxy-piperidin-1-yl)-icosa-5,8,11,14-tetraen-1-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 4515 - 4519

8
[ 50-00-0 ]
[ 64051-79-2 ]
[ 98-86-2 ]
(3-hydroxypiperidin-1-yl)-1-phenylpropan-1-one hydrochloride [ No CAS ]

Reference： [1]Journal of Pharmacy and Pharmacology,1998,vol. 50,p. 583 - 591

9
[ 64051-79-2 ]
[ 98-59-9 ]
[ 220384-68-9 ]

Reference： [1]Journal of the American Chemical Society,1999,vol. 121,p. 700 - 709

10
[ 64051-79-2 ]
[ 1694-92-4 ]
[ 267666-12-6 ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 2444 - 2457

11
[ 64051-79-2 ]
[ 98-09-9 ]
[ 267666-10-4 ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 2444 - 2457

12
[ 64051-79-2 ]
[ 1939-99-7 ]
1-benzenesulfonylmethyl-piperidin-3-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 2444 - 2457

13
[ 24424-99-5 ]
[ 64051-79-2 ]
[ 85275-45-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine; In dichloromethane; at 20℃; for 2h;	Preparation Example 1 : Synthesis of 2,4-bis-trifluoromethyl-5,6.,7.8- tetrahydropyrido [3 ,4-d]pyrimidine hydrochloride(O Synthesis of S-hydroxy-piperidine-l-carboxylic acid t-butyl ester1.0 equivalent of dibutyl dicarbonate (159 g) in 200 mL of methylene chloride were slowly added to a mixture of 3 -hydroxy piperidine hydrochloride (100 g, 0.73 mol) and 1.1 equivalents of triethylamine (111 mL) in methylene chloride(800 mL) at room temperature. Then, the resulting mixture was stirred additionally for 2 hours. After the reaction was complete, the reaction solution was washed with a 1.0 N hydrochloric acid aqueous solution (1.0 L) and the organic layer was concentrated to give 138 g (yield: 94%) of the title compound as a white solid. <n="38"/>1R NMR(500 MHz, CDCl3) deltal.35-1.55 (HH, m), 1.75 (IH, m), 1.88 (IH, m), 3.08 (2H, m), 3.53(1H, m), 3.73 (2H, br d, J=5.6 Hz).
88%	With triethylamine; In dichloromethane;	Preparation 117: 1,1-dimethylethyl 3-hydroxypiperidine-l-carboxylate To a solution of <strong>[64051-79-2]piperidin-3-ol hydrochloride</strong> salt (10.1 g, 0.1 MMOL) in dichloromethane (30 ML) and triethylamine (13.3 ml, 95.4 MMOL) was added a solution of di-tert-butyl dicarbonate (19.8 g, 90.9 MMOL) dropwise in dichloromethane. Upon completion the reaction mixture was added to diethyl ether (120 ml) washed with hydrochloric acid (1 M) and then with brine. The combined organic extracts were dried (MGS04) and concentrated in vacuo to give the title compound as a light yellow oil (17.7 g, 88%).
	With sodium hydroxide; In 1,4-dioxane; water; at 20℃; for 7h;	Racemic <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (662 mg, 4.81 mmol) was dissolved in a mixed solution of water (2 mL) and 1,4-dioxane (4 mL), and to this solution was added 4N aqueous sodium hydroxide (3 mL). To this solution was added di-t-butyl dicarbonate (1.11mL, 4.81 mmol). After the solution was stirred at room temperature for 7 hours, ethyl acetate was added to the resulting reaction solution for extraction. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to obtain the above protected derivative with Boc (968 mg) as a colorless oil. The resulting protected derivative with Boc (968 mg, 4.81 mmol) was dissolved in N,N-dimethylformamide (5 mL), and then methyl iodide (449 muL, 7.22 mmol) was added thereto. After addition of sodium hydride (231 mg, 60% dispersion in oil, 5.77 mmol) under ice-cooling, the mixture was stirred for 5 minutes at the same temperature. The resulting reaction solution was warmed up to room temperature, and stirred for further 10 hours. After saturated aqueous ammonium chloride solution was added to this solution, it was extracted with a mixed solvent of hexane and ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated in vacuo, and azeotropic evaporation was carried out using toluene. The residue was purified by a column chromatography on silica gel to obtain the above methyl ether derivative (885 mg) as a colorless liquid. The resulting methyl ether derivative (885 mg) was dissolved in chloroform (5 mL), and to this solution was added 4N hydrogen chloride/1,4-dioxane solution (5 mL). The solution was stirred at room temperature for 2 hours, and the resulting reaction solution was concentrated in vacuo to obtain the racemic objective compound [A-22] (596 mg) as a white solid.

Reference： [1]Patent: WO2009/82134,2009,A2 .Location in patent: Page/Page column 36-37
[2]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1645 - 1649
[3]Patent: WO2004/72086,2004,A2 .Location in patent: Page 179
[4]Organic letters,2000,vol. 2,p. 155 - 158
[5]Journal of Medicinal Chemistry,2008,vol. 51,p. 4601 - 4608
[6]Patent: EP1557418,2005,A1 .Location in patent: Page/Page column 192-193

14
[ 64051-79-2 ]
[ 4525-33-1 ]
[ 80613-04-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 0 - 20℃;	B. Synthesis of 5ALA ketals and imines using 3-hydroxypiperidine HCI as starting material.; Synthesis of ketals and oximes can be undertaken as outlined in Figure 3.Figure 3. General synthetic route to hydrolysable 5ALA derivativesA detailed outline of synthesis of one ketal derivative based on the above description is given as follows below. 3.1.1 5-delta-Amino Levulinic Acid Ketal Derivative (5-ALA)4.2.1 Stage 1; Synthesis of 3-Hydroxy-Piperidine-1-Carboxylic Acid Methyl Ester 14 (LBN 557-077); To a mixture of 3-hydroxypiperidine HCI 10 (15.0 g, 0.11 mol, 1.0 eq) in DCM (225 ml. 15 vol) was added Et3N (16.6 g. 0.16 mol, 1.5 eq). To the suspension at 0C was added dimethyldicarbonate (14.6 g, 0.11 mol, 1.0 eq) in DCM (30 ml, 2.0 vol cf sm) over 20 min (Tmax <7C). The mixture was allowed to warm to rt and stirred overnight for 18h. After this time a 1H NMR spectrum (CDCI3) of the crude material showed the reaction mixture to contain 20% sm 10. Further dimethyldicarbonate (2.19 g, 16.3 mmol, 0.15 eq) was added in one portion. After a further 2h at rt the reaction was seen to be complete by 1H NMR spectroscopy. H2O (75 ml, 5.0 vol) was added and the layers separated. The organic layer washed with 10% w/ v citric acid (75 ml, 5.0 vol) and H2O (75 ml. 5.0 vol). The layers were separated and the organic layer dried (MgSO2) filtered and concentrated under reduced pressure providing the title compound 14 557-078-4 (10.0 g, 58% yield) as a clear oil. The combined aq layers were then saturated with NaCI and extracted with DCM (2x 100 ml, 7.0 vol). The combined organic layers were washed with brine (100 ml), dried (MgSO4), filtered and concentrated under reduced pressure. After drying to constant weight provided further 14 557-078-6 (7.00 g, 40% yield).1H NMR (CDCI3, 400MHz): delta 3.70-3.56 (m, 6H)1 3.20-3.10 (m, 2H), 2.80-2.20 (m, 1H), 1.90-1.80 (rn, 2H), 1.50-1.40 (m, 2H)

Reference： [1]Organic Letters,2005,vol. 7,p. 4309 - 4312
[2]Patent: WO2010/24775,2010,A1 .Location in patent: Page/Page column 21; 23

15
[ 20850-43-5 ]
[ 64051-79-2 ]
1-(benzo[d][1,3]dioxol-5-ylmethyl)piperidin-3-ol [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2499 - 2504

16
[ 76-83-5 ]
[ 64051-79-2 ]
[ 647863-16-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 0 - 20℃;	To a stirred suspension of 1.37 g (10.0 mmol) of <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> and 2.53 g (3.5 [ML)] of triethylamine in 30 mL of dichloromethane at 0 [C] was added dropwise 2.93 g (10.5 mmol) of trityl chloride. The mixture was stirred at ambient temperature overnight, diluted with 100 mL of dichloromethane, washed sequentially with water, 5% aqueous citric acid solution, saturated sodium bicarbonate solution, and brine, dried over sodium sulfate, and concentrated to give 3.85 g of the title compound as a white foam.

Reference： [1]Patent: WO2004/7468,2004,A1 .Location in patent: Page 56

17
[ 851548-79-3 ]
[ 64051-79-2 ]
α-[5-bromo-2-[[4-[[4-[(3-nitrophenyl)sulfonyl]-1-piperazinyl]carbonyl]phenyl]methoxy]phenyl]-3-hydroxy-1-piperidineethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 2-bromo-1-[5-bromo-2-[[4-[[4-[(3-nitrophenyl)sulfonyl]-1-piperazinyl]carbonyl]phenyl]methoxy]phenyl]ethanone (300 mg, 0.47 mmol) in DMF (5 mL), 3-hydroxypiperidine.HCl (330 mg, 2.4 mmol) and K2CO3 (300 mg) were added at rt. After 1 h, the mixture was poured into ice-water. The solid was collected by filtration, and re-dissolved in MeOH (15 mL). To this solution was added NaBH4 (100 mg) and the mixture was kept at rt overnight. After removal of MeOH, the residue was diluted with EtOAc, washed with brine; dried over Na2SO4, and concentrated. The residue was purified by HPLC to afford the product as a white powder. 1H NMR (DMSO-d6/TFA): delta 1.102.00 (m, 4H), 2.604.00 (m, 15H), 5.105.20 (m, 2H), 5.255.35 (m, 1H), 7.047.14 (m, 1H), 7.267.56 (m, 6H), 7.867.98 (m, 1H), 8.108.18 (m, 1H), 8.328.38 (m, 1H), 8.488.60 (m, 1H).

Reference： [1]Patent: US2005/101644,2005,A1 .Location in patent: Page/Page column 42

18
[ 50921-39-6 ]
[ 96042-30-7 ]
[ 64051-79-2 ]
[ 405087-57-2 ]

Yield	Reaction Conditions	Operation in experiment
82%	With IPr2NEt; In ethyl acetate; Petroleum ether;	Example 72 Synthesis of 1-[1(4-Chloro-phenyl)-cyclobutylmethyl]-3-(4-trifluoromethyl-benzyloxy)-piperidine Amide 88 was prepared from commercially-available <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> and 1-(4-chloro-phenyl)-cyclobutane carboxylic acid, using the procedure outlined for the synthesis of 1 in Example 1:<strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (1.0 g, 7.29 mmol), 1-(4-chlorophenyl)-1-cyclobutane carboxylic acid (2.29 g, 10.9 mmol), PyBroP (5.08 g, 10.9 mmol), iPr2NEt (6.33 mL, 36.3 mmol), DCM (40 mL). Purification by flash column chromatography using 40% ethyl acetate/petroleum ether provided the desired amide 88 (1.74 g, 82%). 13C NMR (75 Mz, CDCl3): delta(major rotamer only) 174.4, 141.9, 132.1, 128.9, 126.4, 65.8, 51.9, 49.3, 45.5, 32.6, 31.9, 22.0, 15.2.
82%	With IPr2NEt; In ethyl acetate; Petroleum ether;	EXAMPLE 72 Synthesis of 1-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-3-(4-trifluoromethyl-benzyloxy)-piperidine Amide 88 was prepared from commercially-available <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> and 1-(4-chloro-phenyl)-cyclobutane carboxylic acid, using the procedure outlined for the synthesis of 1 in Example 1: <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (1.0 g, 7.29 mmol), 1-(4-chlorophenyl)-1-cyclobutane carboxylic acid (2.29 g, 10.9 mmol), PyBroP (5.08 g, 10.9 mmol), iPr2NEt (6.33 mL, 36.3 mmol), DCM (40 mL). Purification by flash column chromatography using 40% ethyl acetate/petroleum ether provided the desired amide 88 (1.74 g, 82%). 13C NMR (75 MHz, CDCl3): delta (major rotamer only) 174.4, 141.9, 132.1, 128.9, 126.4, 65.8, 51.9, 49.3, 45.5, 32.6, 31.9, 22.0, 15.2.

Reference： [1]Patent: US2003/50309,2003,A1
[2]Patent: US2005/80078,2005,A1

19
[ 50921-39-6 ]
[ 64051-79-2 ]
[ 405087-38-9 ]

Yield	Reaction Conditions	Operation in experiment
54%	With aqueous KOH; ammonia; In ethanol; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; toluene;	Example 50 Synthesis of 1-[1-(4-Chlorophenyl)cyclobutylmethyl]piperidin-3-ol (89). The synthesis of amide 88 from commercially-available <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> and 1-(4-chloro-phenyl)-cyclobutanecarboxylic acid is described in Example 72. To amide 88 (100 mg, 0.34 mmol) in toluene (1 mL) was cautiously added Red-A1(0.36 mL, 1.2 mmol). The resulting solution was allowed to stir at room temperature for one and one half hours before diluting with ethyl acetate and quenching with 10% aqueous KOH. The layers were separated and the aqueous layer further washed with ethyl acetate. The combined organic layers were then dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by flash column chromatography using 4% 2M NH3 in EtOH/DCM to provide the desired amine 89 (51 mg, 54%). LRMS calculated for C16H22ClNO 279.14, found (M+) 280.87. 1H NMR (300 MHz, CDCl3): 7.28 (d, J=8.3 Hz, 2H), 7.11 (d, J=8.3 Hz, 2H), 3.67-3.69 (m, 1H), 2.73 (m, 1H), 2.66 (s, 2H), 2.14-2.44 (m, 7H), 1.97-2.11 (m, 2H), 1.79-1.90 (m, 1H), 1.24-1.66 (m, 4H). 13C NMR (75 MHz, CDCl3): 147.6, 131.1, 127.9, 127.4, 68.2, 66.0, 62.2, 55.3, 46.9, 31.8, 31.7, 30.8, 21.2, 16.0.
54%	With aqueous KOH; ammonia; In toluene;	EXAMPLE 50 Synthesis of 1-[1-(4-Chlorophenyl)cyclobutylmethyl]piperidin-3-ol (89). The synthesis of amide 88 from commercially-available <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> and 1-(4-chloro-phenyl)-cyclobutanecarboxylic acid is described in Example 72. To amide 88 (100 mg, 0.34 mmol) in toluene (1 mL) was cautiously added Red-Al (0.36 mL, 1.2 mmol). The resulting solution was allowed to stir at room temperature for one and one half hours before diluting with ethyl acetate and quenching with 10% aqueous KOH. The layers were separated and the aqueous layer further washed with ethyl acetate. The combined organic layers were then dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by flash column chromatography using 4% 2M NH3 in EtOHIDCM to provide the desired amine 89 (51 mg, 54%). LRMS calculated for C16H22ClNO 279.14, found (M+) 280.87. 1H NMR (300 MHz, CDCl3): 7.28 (d, J=8.3 Hz, 2H), 7.11 (d, J=8.3 Hz, 2H), 3.67-3.69 (m, 1H), 2.73 (m, 1H), 2.66 (s, 2H), 2.14-2.44 (m, 7H), 1.97-2.11 (m, 2H), 1.79-1.90 (m, 1H), 1.24-1.66 (m, 4H). 13C NMR (75 MHz, CDCl3): 147.6, 131.1, 127.9, 127.4, 68.2, 66.0, 62.2, 55.3, 46.9, 31.8, 31.7, 30.8, 21.2, 16.0.

Reference： [1]Patent: US2003/50309,2003,A1
[2]Patent: US2005/80078,2005,A1

20
[ 34619-03-9 ]
[ 64051-79-2 ]
[ 85275-45-2 ]
3-(3,4-dichlorophenyl)-3-hydroxy piperidine-1-carboxylic acid {4-[(2,2-dimethyl-propionylamino)-methyl]-phenyl}-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In 1,4-dioxane; hexane; ethyl acetate;	EXAMPLE 9 3-(3,4-dichlorophenyl)-3-hydroxy piperidine-1-carboxylic acid {4-[(2,2-dimethyl-propionylamino)-methyl]-phenyl}-amide To a solution of <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (827 mg, 6 mmol) in dioxane (12 ml) and water (6 ml) cooled to 0 C. is added 1 N NaOH (12 ml, 12 mmol) and dit-butyl carbonate (827 mg, 6 mmol) in dioxane (35 ml) and the reaction mixture is stirred at 25 C. for 1 hr. The reaction mixture is diluted with ethyl acetate, washed with aqueous sodium bicarbonate, 1 N KHSO4, water and brine, dried over sodium sulfate and concentrated in vacuo. The crude product is purified by flash chromatography (silica gel, 50% ethyl acetate in hexane) to give N-t-butoxycarbonyl-3-hydroxypiperidine (1.07 g).

Reference： [1]Patent: US2001/44454,2001,A1

21
[ 1635-61-6 ]
[ 64051-79-2 ]
5-(3'-hydroxypiperidin-1'-yl)-2-nitroaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With potassium carbonate; In N,N-dimethyl-formamide;	EXAMPLE 21 1-(3-Amino-4-nitrophenyl)-piperidin-3-ol A mixture of 5-chloro-2-nitrophenylamine (1.3 g, 7.0 mmol), <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (3.0 g, 20 mmol), and K2CO3 (3.0 g, 22 mmol) in DMF (10 mL) was stirred at 120 C. for 18 h. The reaction mixture was cooled to room temperature, poured into water (100 mL) and extracted with EtOAc (3100 mL). The combined organic extracts were dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography (silica gel, 47.5 cm, eluted with 50:50 CHCl3/EtOAc) to yield the product as an orange solid (0.89 g, 54%). 1H NMR (90 MHz, d6-DMSO/CDCl3) delta7.77 (d, J=9.0 Hz, 1H), 6.25-6.00 (m, 2H), 3.82-3.25 (m, 3H), 3.02-2.62 (m, 2H), 1.90-1.12 (m, 4H).

Reference： [1]Patent: US2002/165218,2002,A1

22
[ 1072-72-6 ]
[ 64051-79-2 ]
[ 217302-10-8 ]

Yield	Reaction Conditions	Operation in experiment
	In water;	Stage 13a: 4-(3-hydroxypiperidino)-tetrahydro-4H-thiopyran-4-carbonitrile <strong>[64051-79-2]3-hydroxy-piperidine hydrochloride</strong> (6.5 g, 47.3 mmoles) in 30 ml of water is introduced into a 100 ml two-necked flask. Potassium cyanide (1.85 g, 35.5 mmoles) is added and tetrahydro-4H-thiopyran-4-one (2.7 g, 23.6 mmoles) is introduced dropwise. The pH of the medium is adjusted to 11 with a few drops of soda (10%). After 24 hours under agitation at ambient temperature, extraction with ether (3*80 ml) is carried out, the combined organic phases are washed with water (100 ml), dried over Na2SO4, filtered and concentrated to dryness. In this way, a colourless oil is obtained (3.9 g, 17.2 mmoles). NMR 13C: 117.87 (CN); 66.25 (Cbeta); 59.19 (C4); 53.20; 45.96 (Calpha'); 33.94 (C3-C5); 31.79 (Cgamma); 22.70 (C2-C6); 21.90 ((Cbeta').

Reference： [1]Patent: US6342511,2002,B1

23
[ 127263-91-6 ]
[ 64051-79-2 ]
[ 105-36-2 ]
[ 200273-74-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; In ethyl acetate; acetonitrile;	EXAMPLE 1 Synthesis of 3-bis(4-fluorophenyl)methoxypiperidin-1-yl acetic acid ethyl ester (Compound C5) A mixture of 0.170 g (0.5 mmol) of 3-bis(4-fluorophenyl)methoxypiperidine [prepared in three steps from <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (Aldrich) using the synthetic scheme described by E. Falch, P. Krogsgaard-Larsen, Eur. J. Med. Chem. 1991, 26, 69-78, for the synthesis of 3-diphenylmethoxypiperidine], 0.092 g (0.55 mmol) ethyl bromoacetate (Aldrich) and 0.276 g (2 mmol) potassium carbonate in 1 ml acetonitrile was stirred under argon for 20 hours. The reaction mixture was filtered, the solvent evaporated and the residue purified by preparative TLC with 30% ethyl acetate in hexanes to give 0.150 g (yield 77%) 3-bis(4-fluorophenyl) methoxypiperidin-1-yl acetic acid ethyl ester (compound C5) as an oil. NMR spectra of the product showed: 1 H NMR (CDCl3, 300 MHz) delta 7.60-7.35 (m, 4 H), 7.35-7.00 (m, 4 H), 5.72 (s, 1 H), 4.38 (q, 2 H), 3.90-3.65 (m, 1 H), 3.42 (br. s, 2 H), 3.25 (d, 1 H), 2.97 (d, 1 H), 2.42 (dt, 2 H), 2.17 (d, 1 H), 2.00-1.80 (m, 1 H), 1.70 (dt, 1 H), 1.60-1.50 (m, 1 H), 1.46 (t, 3 H), 13 C NMR (CDCl3, 75 MHz) delta 170.16, 163.52, 160.27, 138.14, 138.11, 128.50, 128.40, 115.13, 114.85, 79.30, 72.45, 60.27, 59.31, 57.83, 52.80, 30.06, 23.12, 14.01.

Reference： [1]Patent: US6001854,1999,A

24
[ 13734-34-4 ]
[ 64051-79-2 ]
[(1S)-Benzyl-2-((3RS)-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 79b [(1S)-Benzyl-2-((3RS)-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester BOC-L-phenylalanine (8.17 g, 30.8 mmol) and <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (4.24 g, 30.8 mmol) were coupled according to procedure A, giving the title compound as an oil which was used without further purification. Yield 7.79 g, 73%.
		Example 79b [(1S)-Benzyl-2-((3RS)-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester BOC-L-Phenylalanine (8.17 g, 30.8 mmol) and <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (4.24 g, 30.8 mmol) were coupled according to procedure A, giving the title compound as an oil which was used without further purification. Yield 7.79 g, 73 %.

Reference： [1]Patent: US6107329,2000,A
[2]Patent: EP1134213,2001,A2

25
[ 24424-99-5 ]
[ 64051-79-2 ]
1-tert-Butyloxyhydroxypiperidine [ No CAS ]
1-tert-Butyloxycarbonyl-3-{3-methoxy-4-[4-(2-oxo-4H-benzo[1,3]-oxazin-1-yl)-piperidine-1-carbonyl]-phenoxy}-piperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide;	EXAMPLE 143 1-tert-Butyloxycarbonyl-3-{3-methoxy-4-[4-(2-oxo-4H-benzo[1,3]-oxazin-1-yl)-piperidine-1-carbonyl]-phenoxy}-piperidine STR163 Step 1 To a stirred solution of <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (5.0 g, 36.3 mmol) in DMF (100 mL) was added DIEA (7.0 mL, 40.0 mmol). The solution was cooled to 0 C., and di-tertbutyldicarbonate (7.14 g, 32.7 mmol) was added to the reaction mixture. The reaction was stirred for 6 hours and then warmed to ambient temperature. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate, washed with 5% citric acid (75 mL), and water (75 mL). The organic layer was dried (MgSO4), filtered, and the solvent was evaporated under reduced pressure. 1-tert-Butyloxyhydroxypiperidine was obtained as a white solid and used without further purification. TLC: Rf=0.53 in 3% methanol in methylene chloride FAB MS m/z 202 (M++H)

Reference： [1]Patent: US5665719,1997,A

26
[ 64051-79-2 ]
[ 1885-14-9 ]
[ 95798-22-4 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane;	(i) Benzylchloroformate (15 ml) was added dropwise to a stirred suspension of <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (13.7 g) and triethylamine (30 ml) in dichloromethane (150 ml), maintaining the temperature below 15 C. throughout. Stirring was continued for three hours, then the solution was washed with water (4100 ml) and saturated aqueous sodium chloride (100 ml), dried (PS paper) and concentrated. The residual oil was dissolved in ether (300 ml), washed with dilute hydrochloric acid (2100 ml) and water (100 ml), dried (PS paper) and concentrated. The residue was purified by flash column chromatography, eluding first with hexane/ether (1:1) then ether to give 1-benzyloxycarbonylpiperidine-3-ol (7.1 g) as a colourless oil. NMR(d6 DMSO): delta 1.2-1.4(2H,m); 1.6-1.9(1H,m+1H,m); 2.8(1H,br s); 2.95(1H,m); 3.45(1H,m); 3.65(1H,br.d); 3.8(1H,dd); 4.85(1H,d); 5.1(2H,s); 7.3(5H,m); m/e 236(M+H)+.

Reference： [1]Patent: US5753659,1998,A

27
[ 64051-79-2 ]
[ 100-44-7 ]
[ 14813-01-5 ]

Yield	Reaction Conditions	Operation in experiment
56.9%	With triethylamine; In toluene;	REFERENCE EXAMPLE 4 A mixture of 15.0 g of 3-hydroxypiperidine hydrochloride, 13.8 g of benzyl chloride, 22.1 g of triethylamine and 120 ml of toluene was stirred at reflux for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated and distilled under reduced pressure to obtain 11.8 g of 1-benzyl-3-hydroxypiperidine (yield: 56.9%). b.p.: 125-126 C./3.5 mmHg NMR spectrum (CCl4, delta): 1.30-1.90(4H, broad), 2.20-2.50(4H, broad), 3.45(2H, s), 3.40-3.90(1H, broad), 7.20(5H, s)

Reference： [1]Patent: US4448964,1984,A

28
[ 369-34-6 ]
[ 64051-79-2 ]
[ 916988-48-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In N,N-dimethyl-formamide; at 50 - 60℃; for 3h;	A solution of <strong>[64051-79-2]3-hydroxypiperidine hydrochloride</strong> (1.0 g, 7.267 mmol), 3, 4- difluoronitrobenzene (1.15 g, 7.267 mmol) and K2CO3 (1.205 g, 8.72 mmol) in anhydrous DMF was stirred at 50-60 0C for 3 h. At the end of this period TLC showed complete reaction. The mixture was diluted with water (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with saturated solution of NaCl (50 mL), dried (Na2SO4), filtered, and the solvent was removed under reduced pressure to afford desired product in quantitative yield. The product was used without further purification. GC-MS m/z 240 [M+].

Reference： [1]Patent: WO2006/135383,2006,A2 .Location in patent: Page/Page column 94

29
[ 2622-89-1 ]
[ 64051-79-2 ]
[ 207730-16-3 ]

Reference： [1]Journal of Organometallic Chemistry,1998,vol. 553,p. 221 - 239
[2]Journal of Organometallic Chemistry,1998,vol. 553,p. 221 - 239

30
[ 64051-79-2 ]
[ 350-46-9 ]
[ 99841-68-6 ]

Yield	Reaction Conditions	Operation in experiment
51%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; for 18h;Heating / reflux;	a) 4-(3-Hydroxypiperidin-1 -yl)nitrobenzeneTo a solution of 4-fluoronitrobenzene (1 g, 7.09 mmol) in AcN (16 ml_), 3- hydroxypipehdine hydrochloride (1.04 g, 7.57 mmol) and DIEA (1.32 ml_, 7.57 mmol) were added. The mixture was stirred and refluxed for 18 h. The resulting mixture was cooled until room temperature and evaporated. The crude product thus obtained was chromatographed over silica gel using Hexane/EtOAc mixtures of increasing polarity as eluent, to afford 1.15 g of the desired compound (51 % yield).
51%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; for 18h;Heating / reflux;	To a 4-fluoronitrobenzene solution (1 g, 7.09 mmol) in AcN (16 mL), 3- hydroxypipehdine hydrochloride (1.04 g, 7.57 mmol) and DIEA (1.32 mL, 7.57 mmol) were added. The mixture was stirred and refluxed for 18 h. The resulting mixture was cooled until room temperature and concentrated to dryness. The crude product obtained was chromatographed over silica gel using hexane/EtOAc <n="67"/>mixtures of increasing polarity as eluent, to afford 1.15 g of the desired compound (51 % yield).

Reference： [1]Patent: WO2008/90181,2008,A1 .Location in patent: Page/Page column 65
[2]Patent: WO2008/119792,2008,A1 .Location in patent: Page/Page column 65-66

31
[ 14371-10-9 ]
[ 64051-79-2 ]
[ 1082074-99-4 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 8829 - 8837

32
[ 1357306-02-5 ]
[ 64051-79-2 ]
[ 1357305-59-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; for 1h;	General procedure: The crude intermediate was redissolved in DCM (10 mL), and piperidine (159 muL, 137 mg, 1.611 mmol) added, followed by triethylamine (225 muL, 163 mg, 1.611 mmol). After 1 hr, the reaction mixture was concentrated in vacuo, and purified by flash chromatography (SiO2; 20 g pre-packed column) eluting with 50% EtOAc - isohexane to give the urea 9 (470 mg, 50%) as a yellow gum.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 901 - 906

33
[ 394-47-8 ]
[ 64051-79-2 ]
[ 1246816-21-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In dimethyl sulfoxide; at 110℃; for 12h;	A mixture of 2-fluorobenzonitrile (24) (401 mg, 3.31 mmol), (+/-)-<strong>[64051-79-2]piperidin-3-ol hydrochloride</strong> (25) (500 mg, 3.65 mmol) and potassium carbonate (1 .37g, 9.9 mmol) in 10 ml_ DMSO was stirred at 1 10C for 12 hours. The reaction mixture was diluted with ethyl acetate and washed with sat. NaHC03, water and brine. The organic layer was dried over magnesium sulfate, filtered and reduced to dryness. The crude product was purified by silica gel chromatography to afford (+/-)-2-(3-hydroxypiperidin-1 - yl)benzonitrile (26). 1 H NMR (400MHz, CDCI3) delta 7.56 (dd, J = 8.0, 2.0 Hz, 1 H), 7.51 - 7.46 (m, 1 H), 7.05-7.01 (m, 2H), 4.02 (brs, 1 H), 3.31 (dd, J = 1 1 .6, 3.2 Hz, 1 H), 3.13-3.05 (m, 3H), 2.06-1 .98 (m, 1 H), 1 .87-1 .60 (m, 4H). MS m/z 203.1 (M+1 )+.

Reference： [1]Patent: WO2013/33620,2013,A1 .Location in patent: Page/Page column 82

34
[ 1448706-39-5 ]
[ 64051-79-2 ]
[ 1448706-03-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 4608 - 4616

35
[ 64051-79-2 ]
[ 501-53-1 ]
[ 95798-22-4 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium carbonate; In tetrahydrofuran; water; at 20℃; for 5h;	To a solution 5-A (10.00 g, 73 mmol) in THF/H20 (50 mL/50 ml_), was added Na2C03 (23.10 g, 218 mmol). CbzCI (14.90 g, 87 mmol) was added dropwise and the reaction stirred at rt for 5h. The mixture was extracted with EtOAc (100 mL x 3) and the combined the organic layers washed with brine, dried ( gS04), filtered and concentrated. The residue obtained was purified by silica gel column chromatography with EtOAc/Pet ether=1/100~1/4 to give 5-B (16.50 g 96 %) as a colorless oil. TLC: Rf=0.65 silica gel EtOAc/Pet ether=1/1 v/v
95%	With triethylamine; In dichloromethane; at 0℃; for 19h;	10 Step 4: preparation of 3-Hydroxy-piperidine-1-carboxylic acid benzyl ester. Tosuspension of <strong>[64051-79-2]piperidin-3-ol hydrochloride</strong> (134 g, 0.974 mol) and triethylamine (276 mL, 1.98 mol) in dichloromethane (2 L) at 0 C was added a solution of benzyl chloroformate (140 mL, 0.981 mol) in dichloromethane (100 mL) drop wise over 2.5 h. The reaction was allowed to stir for an additional 30 mm at 0 C, then allowed to warm15 to ambient temperature over 16 h, after which it was quenched with 1 N hydrochloric acid (3 L) and allowed to stir for 30 mm. The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo to afford the title compound (218 g, 95 %).1H-NMR (CDCI3) 67.29-7.41 (m, 5H), 5.14 (s, 2H), 3.59-3.85 (m, 3H), 3.13-3.27 (m, 2H), 2.18 (bs, 1H), 1.74-1.94 (m, 2H), 1.38-1.61 (m, 2H).

Reference： [1]Patent: WO2014/32,2014,A1 .Location in patent: Page/Page column 44; 45
[2]Patent: WO2014/68527,2014,A1 .Location in patent: Page/Page column 75; 15

36
[ 1610520-29-0 ]
[ 64051-79-2 ]
[ 1610521-18-0 ]

Yield	Reaction Conditions	Operation in experiment
45.9%		Piperidin-3-ol hydrochloride (0.759 g, 5.51 mmol) was added to a suspension 7-bromo-5-methyl-4- oxo-4,5-dihydrothieno[3,2-c]pyridine-2-carbaldehyde (Intermediate 3) (1 g, 3.67 mmol) in MeOH (18 ml.) and acetic acid (2 ml.) and the mixture was stirred for 30 min at rt. 2-Picoline-borane complex (0.590 g, 5.51 mmol) was added and the reaction was stirred o/n. The reaction was heated to 50C and stirred for 4 hr. The solvent was evaporated and sodium bicarbonate was added (30 ml_). The residue was extracted with DCM (3 x 20 ml_). The extracts were dried by filtration through a hydrophobic frit and then concentrated in vacuo to give the crude product which was purified by silica gel column chromatography [0-5% MeOH in DCM]. Fractions containing pure product were concentrated in vacuo. Fractions containing a mixture of compounds were combined and concentrated in vacuo then purified by silica gel column chromatography [5% MeOH in DCM]. All pure product containing fractions were combined to give the title compound as a yellow solid 7- bromo-2-((3-hydroxypiperidin-1-yl)methyl)-5-methylthieno[3,2-c]pyridin-4(5H)-one (603 mg, 1 .688 mmol, 45.9 % yield). LCMS (2 min, Formic Acid): Rt = 0.49 min, MH+ = 357/359.

Reference： [1]Patent: WO2014/78257,2014,A1 .Location in patent: Page/Page column 122

37
[ 64051-79-2 ]
[ 79-10-7 ]
(S)-1-(3-hydroxypiperidin-1-yl)prop-2-en-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2 g		N,N-dicyclohexylcarbodiimide (8.98 gms) was slowly added to a mixture of acrylic acid (2.61 gms) and dichloromethane (25 ml) at 0-5C. Dimethylaminopyridine (0.21 gms) was added to the reaction mixture at 0-5C and stirred for 60 minutes at the same temperature. A mixture of 3-hydroxy piperidine hydrochloride (5 gms) and dichloromethane,(15 ml) was added to the reaction mixture at 0-5C. Diisopropylethylamine (14.1 gms) was slowly added to the reaction mixture at 0-5C. Raised the reaction mixture temperature to 25- 30C and stirred for 90 minutes at the same temperature. Filtered the reaction mixture and washed with dichloromethane. The obtained filtrate was washed with 2% hydrochloride solution. Both the organic and aqueous layers were seperated and organic layer was washedwith 2% sodium bicarbonate solution and followed by water. Distilled off the solvent completely from the organic layer to get the title compound.Yield: 2.0 gms.

Reference： [1]Patent: WO2016/170545,2016,A1 .Location in patent: Page/Page column 38

38
[ 876-08-4 ]
[ 64051-79-2 ]
(4-(chloromethyl)phenyl)(3-hydroxypiperidin-1-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.62 g	With triethylamine; In dichloromethane; at 0℃; for 0.5h;	To a suspension of 4-(chloromethyl)benzoyl chloride (1 g, 5.29 mmol) and <strong>[64051-79-2]piperidin-3-ol hydrochloride</strong> (0.728 g, 5.29 mmol) in DCM (20 ml) was added drop-wise TEA (0.811 nil, 5.82 mmol) at 0 C. The reaction mixture was stirred at 0 C for 30 mm.Water was added to the mixture, the layers were separated, and the aqueous layer was extracted with DCM. The organic layers were combined, washed with 1 M NaOH, 1 M HC1 and brine, dried with Na2SO4, filtered, and evaporated. Heptane was added to the residue followed by stirring, filtration, and drying to afford the title compound (0.62 g).LC-MS: m/z 254.2 (M+H) .

Reference： [1]Patent: WO2018/115591,2018,A1 .Location in patent: Page/Page column 113

39
[ 64051-79-2 ]
C₅H₁₀ClNO [ No CAS ]

Reference： [1]Nature Chemistry,2019

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P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 64051-79-2 ] {[proInfo.proName]}

Quality Control of [ 64051-79-2 ]

Related Doc. of [ 64051-79-2 ]

Product Details of [ 64051-79-2 ]

Calculated chemistry of [ 64051-79-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 64051-79-2 ]

Application In Synthesis of [ 64051-79-2 ]

[ 64051-79-2 ] Synthesis Path-Upstream 1~5

[ 64051-79-2 ] Synthesis Path-Downstream 1~39

Related Functional Groups of [ 64051-79-2 ]

Alcohols

Related Parent Nucleus of [ 64051-79-2 ]

Aliphatic Heterocycles

Piperidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 64051-79-2 ]

Related Parent Nucleus of
[ 64051-79-2 ]