[ CAS No. 55695-51-7 ] {[proInfo.proName]}

Name: 55695-51-7|(4-Chlorophenyl)(piperidin-4-yl)methanone hydrochloride|97%
Brand: Ambeed
SKU: A123141
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2D 3D

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Quality Control of [ 55695-51-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 55695-51-7 ]

SDS Specification

Alternatived Products of [ 55695-51-7 ]

Product Details of [ 55695-51-7 ]

CAS No. :	55695-51-7	MDL No. :	MFCD00053028
Formula :	C₁₂H₁₅Cl₂NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LZUYKOBTHSPKED-UHFFFAOYSA-N
M.W :	260.16	Pubchem ID :	2777114
Synonyms :

Calculated chemistry of [ 55695-51-7 ]

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.42
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	72.44
TPSA :	29.1 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.71 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	3.06
Log Po/w (WLOGP) :	2.94
Log Po/w (MLOGP) :	2.46
Log Po/w (SILICOS-IT) :	3.2
Consensus Log Po/w :	2.33

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.53
Solubility :	0.0774 mg/ml ; 0.000298 mol/l
Class :	Soluble
Log S (Ali) :	-3.34
Solubility :	0.12 mg/ml ; 0.00046 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.18
Solubility :	0.0173 mg/ml ; 0.0000664 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	1.44

Safety of [ 55695-51-7 ]

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 [ 55695-51-7 ]

* 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 [ 55695-51-7 ]
Downstream synthetic route of [ 55695-51-7 ]

[ 55695-51-7 ] Synthesis Path-Upstream 1~1

1
[ 498-94-2 ]
[ 55695-51-7 ]

Reference： [1] Farmaco, Edizione Scientifica, 1957, vol. 12, p. 853,862

[ 55695-51-7 ] Synthesis Path-Downstream 1~34

1
[ 498-94-2 ]
[ 55695-51-7 ]

Reference： [1]Farmaco, Edizione Scientifica,1957,vol. 12,p. 853,862

2
[ 24424-99-5 ]
[ 55695-51-7 ]
[ 209808-06-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With triethylsilane; In methanol; at 20℃;Inert atmosphere;	Intermediate 40: tert-Butyl 4-(4-chlorobenzoyl)piperidine-1-carboxylate [0689] [0690] Di-tert-butyl dicarbonate (0.923 g, 4.23 mmol) was added to a solution of <strong>[55695-51-7](4-chlorophenyl)(piperidin-4-yl)methanone hydrochloride</strong> (1 g, 3.84 mmol) and triethylamine (1.179 mL, 8.46 mmol) in Methanol (20 mL) under nitrogen. The reaction was stirred at room temperature overnight. The suspension was concentrated in vacuo. The residue was taken up in ethyl acetate and water and the phases separated. The organic was washed with brine, dried (phase separator) and concentrated to give tert-butyl 4-(4-chlorobenzoyl)piperidine-1-carboxylate (1.22 g, 3.77 mmol, 98% yield) as a white solid. [0691] 1H NMR (400 MHz, DMSO-d6) delta ppm 1.33-1.46 (m, 11H) 1.72-1.81 (m, 2H) 2.83-3.00 (m, 2H) 3.62 (s, 1H) 3.92-4.02 (m, 2H) 7.58-7.65 (m, 2H) 7.98-8.04 (m, 2H)
98%	With triethylamine; In methanol; at 20 - 25℃;Inert atmosphere;	Intermediate 40: tert-Butyl 4-(4-chlorobenzoyl)piperidine-l-carboxylate Di-ie/t-butyl dicarbonate (0.923 g, 4.23 mmol) was added to a solution of (4- chlorophenyl)(piperidin-4-yl)methanone hydrochloride (1 g, 3.84 mmol) and triethylamine (1.179 mL , 8.46 mmol) in Methanol (20 mL) under nitrogen. The reaction was stirred at room temperature overnight. The suspension was concentrated in vacuo. The residue was taken up in ethyl acetate and water and the phases separated. The organic was washed with brine, dried (phase separator) and concentrated to give tert-buty 4-(4- chlorobenzoyl)piperidine-l-carboxylate (1.22 g, 3.77 mmol, 98% yield) as a white solid. 1H NMR (400 MHz, DMSO- 6) delta ppm 1.33 - 1.46 (m, 11 H) 1.72 - 1.81 (m, 2 H) 2.83 - 3.00 (m, 2 H) 3.62 (s, 1 H) 3.92 - 4.02 (m, 2 H) 7.58 - 7.65 (m, 2 H) 7.98 - 8.04 (m, 2 H)
98%	With triethylamine; In methanol; at 20℃;Inert atmosphere;	Intermediate 12; tert-Butyl 4-(l-(4-chlorophenyl)-l-hvdroxyethyl)piperidine-l-carboxylateDi-ie/t-butyl dicarbonate (0.923 g, 4.23 mmol) was added to a solution of <strong>[55695-51-7](4-chlorophenyl)(piperidin-4-yl)methanone hydrochloride</strong> (1 g, 3.84 mmol) and triethylamine (1.179 mL , 8.46 mmol) in methanol (20 mL) under nitrogen. The reaction was stirred at room temperature overnight. The suspension was concentrated in vacuo. The residue was taken up in ethyl acetate and water and the phases separated. The organic was washed with brine, dried (phase separator) and concentrated to give tert-butyX 4-(4-chlorobenzoyl)piperidine-l-carboxylate (1.22 g, 3.77 mmol, 98% yield) as a white solid. 1H NMR (400 MHz, DMSO-6) delta ppm 1.33 - 1.46 (m, 11 H) 1.72 - 1.81 (m, 2 H) 2.83 -3.00 (m, 2 H) 3.62 (s, 1 H) 3.92 - 4.02 (m, 2 H) 7.58 - 7.65 (m, 2 H) 7.98 - 8.04 (m, 2 H).Methylmagnesium bromide (3M in ether) (3.09 mL , 9.26 mmol) was added slowly to a solution of tert-butyX 4-(4-chlorobenzoyl)piperidine-l-carboxylate (0.5 g, 1.544 mmol) in THF (10 mL ) at 0 C under nitrogen. The reaction was stirred at room temperature for 2 hours. The reaction was quenched with 2M HCl and partitioned between ethyl acetate and 2M HCl. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organics were washed with saturated brine, dried (phase separator) and concentrated in vacuo to afford tert-butyX 4-(l-(4-chlorophenyl)-l-hydroxyethyl)piperidine- l-carboxylate (0.481 g, 1.415 mmol, 92 % yield) as a colourless oil. MS: ES- 338.

90%	With triethylamine; In acetonitrile; at 20℃; for 16h;	To a mixture of <strong>[55695-51-7](4-chlorophenyl)piperidin-4-ylmethanone hydrochloride</strong> (0.996 g, 3.828 mmol) and triethylamine (2.7 ml, 19.142 mmol) in acetonitrile (15 ml) at room temperature was added di-fert-butyl dicarbonate (1.003 g, 4.594 mmol). After 16 hours at room temperature, the mixture was evaporated to dryness and then partitioned between ethyl acetate (50 ml) and IM hydrochloric acid (20 ml). The organic phase was separated and washed successively with saturated aqueous sodium bicarbonate (20 ml), then brine (20 ml), before being dried over magnesium sulfate and concentrated to dryness. The crude material was purified by silica column chromatography (60% diethyl ether in hexanes) to give the ketone as an oil (1.116 g, 90%). LC/MS: (LCTl) Rt 7.42 [M+H]+ 323.
90%	With triethylamine; In acetonitrile; at 20℃; for 16h;	36B. 4-(4-Chlorobenzoyl)piperidine-l-carboxylic acid fert-butvl ester; To a mixture of <strong>[55695-51-7](4-chlorophenyl)piperidin-4-ylmethanone hydrochloride</strong> (0.996 g, 3.828 mmol) (Maybridge, CDlOOOO) and triethylamine (2.7 ml, 19.142 mmol) in acetonitrile (15 ml) at room temperature was added di-fert-butyl dicarbonate (1.003 g, 4.594 mmol). After 16 hours at room temperature, the mixture was evaporated to EPO <DP n="138"/>dryness and then partitioned between ethyl acetate (50 ml) and IM hydrochloric acid (20 ml). The organic phase was separated and washed successively with saturated aqueous sodium bicarbonate (20 ml), then brine (20 ml), before being dried over magnesium sulphate and concentrated to dryness. The crude material was purified by silica column chromatography (60% diethyl ether in hexanes) to give the ketone as an oil (1.116 g, 90%). LCMS: (LCTl) Rt 7.42 [M+H]+ 323.
90%	With triethylamine; In acetonitrile; at 20℃; for 16h;	EXAMPLE 25; C-4-Chlorophenyl-C-ri-(7H-pyrrolor2.3-d1pyrimidin-4-yl)-piperidin-4-yll-methylamine; 25A. 4-(4-Chlorobenzoyl)piperidine-1-carbochiylic acid ferf-butyl esterTo a mixture of <strong>[55695-51-7](4-chlorophenyl)piperidin-4-ylmethanone hydrochloride</strong> (0.996 g, 3.828 mmol) and triethylamine (2.7 ml, 19.142 mmol) in acetonitrile (15 ml) at room temperature was added di-te/t-butyl dicarbonate (1.003 g, 4.594 mmol). After 16 hours at room temperature, the mixture was evaporated to dryness and then partitioned between ethyl acetate (50 ml) and 1M hydrochloric acid (20 ml). The organic phase was separated and <n="137"/>washed successively with saturated aqueous sodium bicarbonate (20 ml), then brine (20 ml), before being dried over magnesium sulfate and concentrated to dryness. The crude material was purified by silica column chromatography (60% diethyl ether in hexanes) to give the ketone as an oil (1.116 g, 90%). LC/MS: (LCT1) Rt 7.42 [M+H]+ 323.
90%	With triethylamine; In acetonitrile; at 20℃; for 16h;	8A. 4-f4-Chlorobenzoyl)piperidine-l-carboxylic acid ferf-butyl ester; To a mixture of <strong>[55695-51-7](4-chlorophenyl)piperidin-4-ylmethanone hydrochloride</strong> (0.996 g, 3.828 mmol) and triethylamine (2.7 ml, 19.142 mmol) in acetonitrile (15 ml) at room temperature was added di-tert-butyl dicarbonate (1.003 g, 4.594 mmol). After 16 hours at room temperature, the mixture was evaporated to dryness and then partitioned between ethyl acetate (50 ml) and IM hydrochloric acid (20 ml). The organic phase was separated and washed successively with saturated aqueous sodium bicarbonate (20 ml), then brine (20 ml), before being dried over magnesium sulfate and concentrated to dryness. The crude material was purified by silica column chromatography (60% diethyl ether in hexanes) to give the ketone as an oil (1.116 g, 90%). LC/MS: (LCTl) R4 7.42 [M+H]+ 323.

Reference： [1]Patent: US2013/324576,2013,A1 .Location in patent: Paragraph 0689; 0690; 0691
[2]Patent: WO2013/179024,2013,A1 .Location in patent: Page/Page column 67-68
[3]Patent: WO2014/202999,2014,A1 .Location in patent: Page/Page column 39; 40
[4]Journal of Medicinal Chemistry,2008,vol. 51,p. 2147 - 2157
[5]Patent: WO2006/46023,2006,A1 .Location in patent: Page/Page column 137
[6]Patent: WO2006/51290,2006,A2 .Location in patent: Page/Page column 135-136
[7]Patent: WO2007/125315,2007,A2 .Location in patent: Page/Page column 134-135
[8]Patent: WO2007/125320,2007,A1 .Location in patent: Page/Page column 131
[9]Journal of Medicinal Chemistry,2000,vol. 43,p. 3895 - 3905

3
[ 55695-51-7 ]
[ 209807-41-0 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3895 - 3905

4
[ 55695-51-7 ]
[ 209808-08-2 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3895 - 3905

5
[ 98-03-3 ]
[ 55695-51-7 ]
1-(thien-2-ylmethyl)-4-(4-chlorobenzoyl)piperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%		To a stirred suspension of (4-chlorophenyl) (4-piperidyl) methanone hydrochloride (200mg, 0. [82MMOL)] in THF [(6ML)] was added 2-thiophene [CARBOXALDEHYDE (LOLMG,] 0. [90MMOL).] The reaction was stirred at [35C] for 5 hours before the addition of sodium triacetoxyborohydride (434mg, 2. [05MMOL).] The reaction was left to stir at [35C] for 48 hours before quenching by the addition of water [(LOML). VOLATILES] removed under reduced pressure and the resulting solid was partitioned between water and DCM. The DCM layer was separated off and the aqueous was reextracted with DCM. The organic phases were combined and washed with brine, then dried, filtered and evaporated to yield crude product. This crude product was dissolved in DCM and treated with PS-trisamine (60mg) and PS-tosylchloride (290mg) for 12 hours. The polymer bound reagents were filtered off and the solvent was removed to yield the product (98mg, 38%). NMR: 1.85 (m, 4H), 2.00 (m, 2H), 3.00 (m, 2H), 3.20 (m, 1H), 3.75 (s, 2H), 6.95 (m, 2H), 7.25 (m, 1H), 7.40 (d, 2H), 7.85 (d, 2H).

Reference： [1]Patent: WO2004/33427,2004,A1 .Location in patent: Page 101-102

6
[ 55695-51-7 ]
[ 403-43-0 ]
(4-(4-chlorobenzoyl)piperidin-1-yl)(4-fluorophenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	With triethylamine; In dichloromethane; at 20℃; for 1h;	To a stirred solution of (4-chlorophenyl) (4-piperidyl) methanone hydrochloride (187mg, 0. [72MMOL)] and triethylamine (240l, 1. 71mmol) in DCM [(3ML)] was added 4- fluorobenzoyl chloride (109mg, 0. 69mmol). The reaction was left to stir at room temperature for one hour then transferred to a sep funnel and diluted to approximately [10ML] with DCM. This solution was washed with 2M HCI [(5ML),] water (5ml) and brine [(5ML)] then dried, filtered and evaporated to yield product as a solid (70mg, 29%). NMR [(DMSO-D6,] [100C)] : 1.60 (m, 2H), 1.85 (m, 2H), 3.15 (t, 2H), 3.65 (m, 1H), 4.00 (m, 2H), 7.20 (t, 2H), 7.45 (m, 2H), 7.55 (d, 2H), 7.95 (d, 2H); m/z: 346.

Reference： [1]Patent: WO2004/33427,2004,A1 .Location in patent: Page 60

7
[ 16629-19-9 ]
[ 55695-51-7 ]
1-(thien-2-ylsulphonyl)-4-(4-chlorobenzoyl)piperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With triethylamine; In dichloromethane; at 20℃; for 1h;	To a stirred solution of [(4-CHLOROPHENYL) (4-PIPERIDYL)] methanone hydrochloride [(100MG,] 0.41mmol) and triethylamine (104mg, 1.03 mmol) in DCM [(4ML)] was added 2- [THIOPHENESULPHONYL] chloride [(71MG,] [039MMOL).] The reaction was stirred at room temperature for 1 hour then diluted to approximately [10ML] with DCM and transferred to a sep funnel. The solution was then washed with 2M HCI (5ml), water [(5ML)] and brine (5ml), then dried, filtered and evaporated to yield the product as a solid (83mg, 55%). NMR (DMSO-d6) : 1.55 (m, 2H), 1.90 (d, 2H), 2.55 (m, 2H), 3.50 (m, 1H), 3.65 (d, 2H), 7.30 (s, 1H), 7.50 (d, 2H), 7.60 (br s, 1H), 8.00 (d, 2H), 8.05 (m, 1H) ; m/z 370.

Reference： [1]Patent: WO2004/33427,2004,A1 .Location in patent: Page 95

8
[ 3839-22-3 ]
[ 55695-51-7 ]
1-(2-cyanobenzoyl)-4-(4-chlorobenzoyl)piperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%		In a test tube was placed 2-cyanobenzoic acid (49mg, 0.33mmol), [4- (4-] chlorobenzoyl) piperidine hydrochloride (86mg, 0.33mmol), [N-METHYLMORPHOLINE] [(36P, 1,] 0. [33MMOL)] and anhydrous THF [(4ML).] The resulting suspension was stirred at room temperature for 15minutes before the addition [OF 4- (4, 6-DIMETHOXY-1,] 3, [5-TRIAZIN-2-YL)-4-] methylmorpholinium chloride hydrate (106mg, 0. 36mmol). The reaction was left to stir overnight at room temperature then worked up. 1M [HCI (2ML)] was added and the reaction was capped and briefly shaken then allowed to settle. The organic layer was transferred to a 4 dram vial then evaporated to yield crude product. This material was purified by prep LCMS (1-40% over 9. 5mins, MeCN/water, with a constant 5ml/min 4% formic [ACID/MECN)] to yield a solid [(19MG,] 16%). m/z 353.

Reference： [1]Patent: WO2004/33427,2004,A1 .Location in patent: Page 68-69

9
[ 10531-41-6 ]
[ 55695-51-7 ]
[ 654673-72-0 ]

Yield	Reaction Conditions	Operation in experiment
17%	With triethylamine; In dichloromethane; at 20℃; for 1h;	To a stirred suspension of (4-chlorophenyl) (4-piperidyl) methanone hydrochloride [(100MG,] 0.41mmol) in DCM [(5ML)] was added triethylamine (104mg, 1. [03MMOL)] and 2- [BROMO-L- (2-THIENYL)-L-ETHANONE] (76mg, 0. [37MMOL).] The reaction was stirred at room temperature for 1 hour. The crude reaction mixture was transferred to a separating funnel and washed with 2M hydrochloric acid. The organic layer was separated and washed with water then evaporated to yield an impure solid. This material was partitioned between DCM and saturated sodium hydrogencarbonate solution. The organic layer was separated and washed with brine then dried [(MGS04),] filtered and evaporated to give a solid. This solid was dissolved in ether and treated with hydrochloric acid in ether. The resulting solid was filtered off to yield the product as a solid (24mg, 17%). NMR (DMSO-d6): 2.00 [(M,] 4H), 3.20 [(M,] 2H), 3.50 [(M,] 1H), 3.60 [(M,] 2H), 5.00 (s, 2H), 7.35 (s, 1H), 7.60 (d, 2H), 8.05 (d, 2H), 8.10 (s, 1H), 8.20 (d, [1H),] 10.20 (br s, 1H) ; m/z: 348.

Reference： [1]Patent: WO2004/11410,2004,A1 .Location in patent: Page 90

10
di-O,O-benzoyl-L-tartaric acid [ No CAS ]
TBME-isopropanol [ No CAS ]
N-formyl-4-(4-chlorobenzoyl)-piperidine [ No CAS ]
[ 1634-04-4 ]
[ 95715-87-0 ]
[ 55695-51-7 ]
[ 75-36-5 ]
(S)4-[4-(4-Chlorobenzoyl)-piperidin-1-ylmethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester dibenzoyl-L-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium borohydrid; sodium hydrogencarbonate; acetic acid; triethylamine; In water; isopropyl alcohol; toluene;	Method G Preparation of (S)4-[4-(4-Chlorobenzoyl)-piperidin-1-ylmethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester dibenzoyl-L-tartrate (dibasic) To a cooled (0 C.) suspension of sodium borohydride (2.40 g, 63.55 mmol) in dry toluene (50 ml) under an inert gas atmosphere acetic acid (11.45 g, 189.9 mmol) is added over a period of 1 hr. Stirring is continued at ambient temperature for 5 hr, until hydrogen evolution has ceased (=Suspension 1). In a separate flask, 4-(4-chlorobenzoyl)-piperidine hydrochloride (obtained by reaction of N-formyl-4-(4-chlorobenzoyl)-piperidine and acetyl chloride) (5.51 g, 21.18 mmol) is suspended in dry toluene (20 ml) at room temperature. Triethylamine (2.57 g, 25.42 mmol) is added and a toluene solution (55 ml) of (R)4-formyl-2, 2-dimethyl oxazolidine-3-carboxylic acid tert-butyl ester (5.59 g, 24.36 mmol), is added dropwise over a period of 45 min with stirring. Stirring is continued for another 20 min, before Suspension 1 is slowly added with stirring over a period of 60 min. The resulting suspension is stirred at ambient temperature until TLC shows complete consumption of starting material (14 hr), then slowly added to a solution of NaHCO3 (25 g, 297.6 mmol) in water (120 ml). The resulting emulsion is stirred at 20 C. for 60 min, the aqueous phase of the mixture is separated and the organic phase is washed twice successively with 20 ml each of 10% aq. NaHCO3 and water. After adjusting the pH of the combined aqueous phases to 9.5 with solid Na2CO3, the aqueous phases are extracted with toluene (225 ml). Celite (0.5 g) is added to the combined organic phases, which are subsequently filtered and evaporated to dryness to afford the free base, which is taken up in isopropanol (35 ml) and heated to reflux temperature. A solution of di-O,O-benzoyl-L-tartaric acid (4.0 g, 10.6 mmol) in isopropanol (10 ml) is added dropwise. After stirring at 79-81 C. for 20 min, the mixture is cooled, diluted with tert-butyl methyl ether (TBME) and the product crystallized at 0 C., filtered off, washed with a cold (0 C.) 1:2-mixture of TBME-isopropanol (15 ml) and cold (0 C.) TBME (35 ml), and dried under vacuum. Recrystallisation of the dried product from isopropanol followed by drying under vacuum gives the title product as a crystalline solid m p 174 C. MS (ES+): [M]+ 437.

Reference： [1]Patent: US2003/176460,2003,A1

11
[ 288-32-4 ]
[ 60491-16-9 ]
[ 55695-51-7 ]
[ 125700-67-6 ]
[ 141-43-5 ]
[ 389890-69-1 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine; triphenylphosphine; trifluoroacetic acid; In methanol; dichloromethane; N,N-dimethyl-formamide;	Method C Preparation of (E)-3-(5-Bromo-2-methoxy-phenyl)-N-{2-[4-(4-chloro-benzoyl)-piperidin-1-yl]-ethyl}-acrylamide To a suspension of 2-(formyl-3-methoxyphenoxy)ethyl polystyrene (AMEBA) resin (ex Novabiochem) (6.85 g, 3.33 mmol) in a mixture of methanol/dichloromethane (60 ml, 1:1 v/v) is added 2-amino ethanol and sodium triacetoxyborohydride (4.00 g, 18.85 mmol) and the mixture shaken for 16 hours at 20 C., then filtered. The resin is washed with methanol, DMF and dichloromethane, then dried under vacuum. A THF/acetonitrile mixture (50 ml, 1:1 v/v) is added to the dried resin followed by iodine (4.80 g, 18.85 mmol), imidazole (1.28 g, 18.85 mmol) and triphenylphosphine (4.90 g, 18.85 mmol). The suspension obtained is shaken for 18 hours at 20 C., then filtered. The resin is washed with THF and dried under vacuum. To the freshly prepared resin (0.50 g, 0.35 mmol) is added a solution of <strong>[55695-51-7](4-chloro-phenyl)-piperidin4-yl-methanone hydrochloride</strong> (0.18 g, 0.70 mmol) dissolved in DMF (2 ml) and diisopropylethylamine (0.36 g, 2.8 mmol). The mixture is heated at 50 C. for 16 hours and then filtered. The resin is washed with DMF. To the washed resin are added (E)-3-(5-Bromo-2-methoxy-phenyl)-acrylic acid (0.27 g, 1.05 mmol), 2-(1H benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborate (0.34 g, 1.05 mmol), diisopropylethylamine (0.29 g, 1.05 mmol) and DMF (4 ml) and the mixture is shaken at 20 C. for 16 hours, then washed with DMF and methanol, after which it is treated with trifluoroacetic acid/dichloromethane (6 ml, 1:1 v/v) at 20 C. for 1 hour to remove the product from the resin. The resulting mixture is filtered and the filtrate evaporated under vacuum to give the product, [MH]+ 506.7.

Reference： [1]Patent: US2003/176460,2003,A1

12
[ 1670-81-1 ]
[ 55695-51-7 ]
[ 353522-09-5 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; triethylamine; In dichloromethane;	Example 5 Synthesis of [4-(4-Chlorobenzoyl)-piperidin-1-yl]-(1H-indol-5-yl)-methanone (compound 5) Indole-5-carboxylic acid (18 mg, 0.11 mmole) and 4-(4-chlorobenzoyl) piperidine hydrochloride (26 mg, 0.1 mmole) were dissolved in 5 ml dichloromethane. To this solution was added triethylamine (1 eq. to neutralize the HCl salt) catalytic DMAP and EDCI (33 mg, 0.11 mmole). The reaction mxture was stirred at room temperature overnight and then worked up by washing sequentially with 1N HCl, saturated sodium bicarbonate, and saturated sodium chloride. The compound was then purified by flash chromatography on silica gel (40:1 CHCl3/MeOH). 1H NMR (300 Mhz, CDCl3) delta 8.45 (s, 1H), 7.88 (d, 2H), 7.72 (s, 1H), 7.45 (d, 2H), 7.38 (d, 1H), 7.24 (s, 2H), 6.58 (s, 1H), 3.42 (m, 1H), 3.11 (m, 2H), 1.83 (m, 4H), 1.60 (m, 2H).

Reference： [1]Patent: US6372752,2002,B1

13
[ 39684-80-5 ]
[ 55695-51-7 ]
[ 298699-05-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; trifluoroacetic acid; In dichloromethane; water; N,N-dimethyl-formamide;	(i) [1-(2-Aminoethyl)-4-piperidinyl](4chlorophenyl)methanone trifluoroacetate To a solution of <strong>[55695-51-7](4-chlorophenyl)(4-piperidinyl)methanone hydrochloride</strong> (2.5 g) and tert-butyl 2-bromoethylcarbamate (2.1 g) in DMF was added triethylamine (2.9 g), after 72 hours at room temperature water and ether were added. The organic phase was separated, dried and concentrated. The residue was dissolved in dichloromethane (40 ml), trifluoroacetic acid (10 ml) added and the solution left for 20 hours. Evaporation of the solvent gave a sticky solid which was triturated under ether to give the sub-titled product as a solid (2.5 g).

Reference： [1]Patent: US6518286,2003,B1

14
[ 123-51-3 ]
[ 4169-67-9 ]
[ 55695-51-7 ]
1-[3-(2-cinnamoylaminophenylthio)propyl]-4-(4-fluorobenzoyl)piperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;	(c) Synthesis of 1-[3-(2-cinnamoylaminophenylthio)propyl]-4-(4-fluorobenzoyl)piperidine Using 3.17 g (9.58 mmol) of 1-chloro-3-[2-(cinnamoylamino)phenylthio]propane, 2.33 g (9.58 mmol) of <strong>[55695-51-7]4-(4-chlorobenzoyl)piperidine hydrochloride</strong>, 2.76 g (20.0 mmol) of potassium carbonate and 30 ml of isoamyl alcohol as starting materials, the same reaction as Example- 1 was conducted. The product obtained was purified by column chromatography (eluent: chloroform/methanol=40/1) to obtain the above-entitled compound. Yield: 2.97 g (6.10 mmol), 64%. TLC (CHCl3:MeOH=9:1). Rf =0.51. MS (FD, m/z) 502 (M+). 1 H-NMR (TMS/DMSO-d4, delta/ppm) 1.30~2.02 (7H, m), 2.95~3.22 (3H, m), 7.10 (1H, d, J=8, 8Hz), 7.23 (1H, dd, J=8, 8Hz), 7.31 (1H, dd, J=8, 8Hz), 7.39 (1H, dd, J=9, 9Hz), 7.41 (2H, dd, J=8, 8Hz), 7.46 (1H, d, J=8Hz), 7.55 (1H, d, J=8Hz), 7.60 (2H, d, J=18Hz), 7.65 (2H, d, J=8Hz), 7.71 (1H, d, J=8Hz), 8.06 (2H, dd, J=8, 6Hz), 9.64 (1H, s).

Reference： [1]Patent: US5231105,1993,A

15
[ 55695-51-7 ]
[ 501-53-1 ]
[ 885595-17-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In dichloromethane; at 0 - 20℃; for 18h;	To a mixture of <strong>[55695-51-7](4-chlorophenyl)piperidin-4-ylmethanone hydrochloride</strong> (0.752 g, 2.890 mmol) and triethylamine (1.21 ml, 8.670 mmol) in DCM (20 ml) at 0 0C was EPO <DP n="136"/>added benzyl chloroformate (0.495 ml, 3.468 mmol). After 18 hours at room temperature, the mixture was washed with saturated aqueous sodium bicarbonate (25 ml), then brine (25 ml) before being dried over sodium sulfate and concentrated. The crude material was purified by silica column chromatography (ethyl acetate) to give the ketone as an oil (0.934 g, 100%). LC/MS: (LCTl) Rt 7.47 [M+H]+ 357.
100%	With triethylamine; In dichloromethane; at 0 - 20℃; for 18h;	EXAMPLE 24; C-Phenyl-C-ri-(7H-pyrrolor2,3-dlpyrimidin-4-yl)-piperidin-4-vn-methylamine; 24A. 4-(4-Chlorobenzoyl)piperidine-1-carboxylic acid benzyl esterTo a mixture of <strong>[55695-51-7](4-chlorophenyl)piperidin-4-ylmethanone hydrochloride</strong> (0.752 g, 2.890 mmol) and triethylamine (1.21 ml, 8.670 mmol) in DCM (20 ml) at 0 0C was added benzyl chloroformate (0.495 ml, 3.468 mmol). After 18 hours at room temperature, the mixture was washed with saturated aqueous sodium bicarbonate (25 ml), then brine (25 ml) before being dried over sodium sulfate and concentrated. The crude material was purified by silica column chromatography (ethyl acetate) to give the ketone as an oil (0.934 g, 100%). LC/MS: (LCT1 ) Rt 7.47 [M+H]+ 357.

Reference： [1]Patent: WO2006/46023,2006,A1 .Location in patent: Page/Page column 133-134
[2]Patent: WO2007/125315,2007,A2 .Location in patent: Page/Page column 131

Yield	Reaction Conditions	Operation in experiment
		A. By following the manipulative procedures described above in Example 1(c), and (d), 37.4 g of 1-acetylisonipecotoyl chloride, [Example 1(b)] and 40 g of aluminum chloride in 90 ml of chlorobenzene are reacted to produce 4-(4-chlorobenzoyl)piperidine hydrochloride. The salt is recrystallized thrice from an ethanol-ether mixture to give a white product, mp. 233-235 C.
		PREPARATION 4 4-(4-Chlorobenzoyl)piperidine Hydrochloride 4-(4-Chlorobenzoyl)piperidine hydrochloride, m.p. 233-235 C., was prepared according to the procedures of Preparations 1 and 2. Analysis: Calculated for C12 H15 Cl2 NO: C, 55.40; H, 5.81; N, 5.38; Found: C, 55.49; H, 5.84; N, 5.43.

17
[ 3309-00-0 ]
[ 55695-51-7 ]
[ 71-36-3 ]
4-(p-chlorobenzoyl)-1-[3-(p-chlorobenzoyl)propyl]piperidine Hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In hydrogenchloride; ethanol;	EXAMPLE 4 4-(p-chlorobenzoyl)-1-[3-(p-chlorobenzoyl)propyl]piperidine Hydrochloride A mixture of <strong>[55695-51-7]4-(p-chlorobenzoyl)piperidine hydrochloride</strong> (10.5 g.; 0.04 mole), 2-(p-chlorophenyl)-2-(omega-chloropropyl)-1,3-dioxolane (10.5 g.; 0.04 mole) and sodium bicarbonate (13.5 g.; 0.16 mole) of n-butanol was refluxed for twenty hours. The hot mixture was filtered, the filtrate was concentrated at reduced pressure and the residual material was dissolved in a mixture of ethanol and 6N hydrochloric acid. The mixture was stirred 0.5 hour and hydrochloride salt which separated was collected by filtration. The salt was recrystallized from isopropanol-methanol (charcoal) to give 9.2 g. (57%) of the hydrochloride salt which melted at 253-256 C. Analysis: Calculated for C22 H24 Cl3 NO2: C,59.94; H,5.26; N,3.18. Found: C,60.07; H,5.42; N,3.23.

Reference： [1]Patent: US4101662,1978,A

18
[ 215790-29-7 ]
[ 55695-51-7 ]
(trans-4-{2-[4-(4-chloro-benzoyl)-piperidin-1-yl]-ethyl}-cyclohexyl)-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%		Step 1 (trans-4-{2-[4-(4-Chloro-benzoyl)-piperidin-1-yl]-ethyl}-cyclohexyl)-carbamic acid tert-butyl ester From (4-chlorophenyl)(4-piperidyl)methanone hydrochloride (100 mg) and [trans-4-(2-oxo-ethyl)-cyclohexyl]-carbamic acid tert-butyl ester (intermediate C, 102 mg) by procedure A.1. Yield: 128 mg (74%). Light yellow solid. MS (m/z): 449.3 ([M+H]+). ; General Procedure A.1 for the Reductive Amination A mixture of amine hydrochloride (1.0 eq.) and aldehyde (1.1 eq.) in 1,2-dichloroethane (ca. 0.2 M) was stirred over night at room temperature. Na(AcO)3BH (1.5 eq.) was added and the reaction was monitored by TLC and MS. After completion sat. aq. NHCO3 sol. was added and the product was extracted with CH2Cl2. After drying (Na2SO4 or MgSO4) the solvent was evaporated and the product purified by flash chromatography.

Reference： [1]Patent: US2007/197531,2007,A1 .Location in patent: Page/Page column 54-55

19
[ 416852-29-4 ]
[ 32315-10-9 ]
[ 55695-51-7 ]
[ 416849-59-7 ]

Yield	Reaction Conditions	Operation in experiment
55%	With triethylamine; In dichloromethane; at -40 - 20℃; for 50h;	A mixture of compound 48 (0.57 g, 2 mmol) and compound 42 (0.52 g, 2 mmol) in CH2Cl (20 mL) was added Et3N (1.95 mL) and the reaction cooled to - 40C. Triphosgene (0.2 g) was added and the reaction stirred at - 40C for 2 h and room temperature for 48 h. The reaction was then washed with IN NaOH, brine, and the organic layer dried. Concentration gave a residue that was purified by column chromatography (10% MeOH in EtOAc) to provide 49 (0.14 g, 55%).

Reference： [1]Patent: WO2008/108957,2008,A2 .Location in patent: Page/Page column 47

20
[ 55695-51-7 ]
[ 586-75-4 ]
(4-bromophenyl) [4-(4-chlorobenzoyl)piperidin-1-yl]methanane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In tetrahydrofuran; water; at 20℃; for 3h;	To tetrahydrofuran (120 mL) were added 4-bromobenzoyl chloride (25 g), <strong>[55695-51-7](4-chlorophenyl)piperidin-4-ylmethanone hydrochloride</strong> (30 g) and 1N aqueous sodium hydroxide solution (250 mL), and the mixture was stirred at room temperature for 3 hr. Ethyl acetate was added for partitioning, the organic layer was washed with saturated brine, and the solvent was evaporated. The residue was recrystallized to give the title compound (46 g).

Reference： [1]Patent: EP2364975,2011,A1 .Location in patent: Page/Page column 29

21
[ 55695-51-7 ]
[ 586-75-4 ]
[ 1223425-52-2 ]

Reference： [1]Patent: EP2364975,2011,A1

22
[ 6311-35-9 ]
[ 55695-51-7 ]
[ 1223431-66-0 ]

Yield	Reaction Conditions	Operation in experiment
		To chloroform (150 mL) were added (4-chlorophenyl)(piperidin-4-yl)methanone hydrochloride (13 g) and 1N aqueous sodium hydroxide solution (50 mL), and the mixture was stirred at room temperature for 10 min. The chloroform layer was partitioned, methanol (50 mL), <strong>[6311-35-9]6-bromonicotinic acid</strong> (10 g) and 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMT-MM) (16.6 g) were added, and the mixture was stirred at room temperature overnight. After evaporation of the solvent, ethyl acetate was added, and insoluble materials were filtered off. The solvent in the filtrate was evaporated to give the title compound (16.4 g).
16.4 g		[0708] Preparation Example 190: Preparation of (6-bromopyridin-3-yl)[4-(4-chlorobenzoyl)piperidin-1-y1]methanone[0709][0710] (4-Chlorophenyl)(piperidin-4-yl)methanone hydrochloride (13 g) and 1N aqueous sodium hydroxide solution(50 mL) were added to chloroform (150 mL), and the mixture was stirred at room temperature for 10 min. The chloroformlayer was partitioned, to the obtained organic layer were added methanol (50 mL), <strong>[6311-35-9]6-bromonicotinic acid</strong> (10 g) and4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMT-MM) (16.6 g), and the mixture wasstirred at room temperature overnight. The solvent was evaporated from the reaction mixture, ethyl acetate was added,and the insoluble material was collected by filtration. The solvent was evaporated from the obtained filtrate to give thetitle compound (16.4 g).

Reference： [1]Patent: EP2364975,2011,A1 .Location in patent: Page/Page column 28
[2]Patent: EP2565182,2013,A1 .Location in patent: Page/Page column 0708; 0709; 0710

23
[ 1223431-56-8 ]
[ 55695-51-7 ]
[ 1223431-03-5 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; In methanol; chloroform; at 20℃;	To a mixture of (R)-4-(4-isopropyl-2-oxooxazolidin-3-yl)benzoic acid (499 mg) described in Preparation Example 18, <strong>[55695-51-7](4-chlorophenyl)piperidin-4-ylmethanone hydrochloride</strong> (520 mg) and 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMT-MM) (829 mg) were added chloroform (3 mL), methanol (3 mL) and N-methylmorpholine (220 muL), and the mixture was stirred at room temperature overnight. After evaporation of the solvent, the residue was purified by column chromatography (chloroform:methanol) to give the title compound (728 mg).

Reference： [1]Patent: EP2364975,2011,A1 .Location in patent: Page/Page column 29

24
[ 74124-79-1 ]
[ 920-66-1 ]
[ 55695-51-7 ]
[ 1352010-97-9 ]