[ CAS No. 135634-18-3 ] {[proInfo.proName]}

Name: 135634-18-3|(2,4-Difluorophenyl)(piperidin-4-yl)methanone oxime hydrochloride|95%
Brand: Ambeed
SKU: A318166
Price: 11.0 USD
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Quality Control of [ 135634-18-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 135634-18-3 ]

SDS Specification

Alternatived Products of [ 135634-18-3 ]

Product Details of [ 135634-18-3 ]

CAS No. :	135634-18-3	MDL No. :	MFCD11869788
Formula :	C₁₂H₁₅ClF₂N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	276.71	Pubchem ID :	-
Synonyms :

Calculated chemistry of [ 135634-18-3 ]

Physicochemical Properties

Num. heavy atoms :	18
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.42
Num. rotatable bonds :	2
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	71.34
TPSA :	44.62 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) :	-5.94 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	2.89
Log Po/w (WLOGP) :	3.4
Log Po/w (MLOGP) :	2.66
Log Po/w (SILICOS-IT) :	3.07
Consensus Log Po/w :	2.4

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.49
Solubility :	0.0893 mg/ml ; 0.000323 mol/l
Class :	Soluble
Log S (Ali) :	-3.49
Solubility :	0.0901 mg/ml ; 0.000326 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.69
Solubility :	0.0565 mg/ml ; 0.000204 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.36

Safety of [ 135634-18-3 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P201-P202-P260-P264-P270-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P308+P313-P363-P405-P501	UN#:	1759
Hazard Statements:	H302-H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 135634-18-3 ]

* 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 [ 135634-18-3 ]
Downstream synthetic route of [ 135634-18-3 ]

[ 135634-18-3 ] Synthesis Path-Upstream 1~7

1
[ 135634-18-3 ]
[ 106266-06-2 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium carbonate In acetonitrile for 32 h; Heating / reflux	A mixture of 4.75 g of 3- (2-chloroethyl)-6, 7,8, 9-tetrahydro-2-methyl-4H-pyrido [[1,] [2-A] PYRIMIDIN-4-ONE] hydrochloride, 5.1 g of [4- (2,] 4-difluorobenzoyl) piperidine oxime hydrochloride, 0.46 g of potassium iodide, 5 g of anhydrous sodium carbonate and 30 ml of acetonitrile was stirred and refluxed for 32 hours. The reaction mixture was cooled and water (120 ml) was added under stirring. Separated solid stirred at [5° FOR 1] hour, filtered, washed with water and crystallized from ethyl acetate yielding 6 g (81percent) of [3- [2- [4- (6-FLUORO-] [1,] [2-BENZISOXAZOLE-3-YL) PIPERIDINO] ETHYL]-6,] 7,8, [9-TETRAHYDRO-2-METHYL-4H-PYRIDO [ 1,] 2-a] [PYRIMIDIN-4-ONE.]
79%	With potassium carbonate In acetonitrile for 30 h; Heating / reflux	A mixture of 4.75 g of [3-(2-CHLOROETHYL)-6,] 7,8, 9-tetrahydro-2-methyl-4H-pyrido [1, 2-a] pyrimidin-4-one hydrochloride, 5. 1 g of [4- (2, 4-DIFLUOROBENZOYL)] piperidine oxime hydrochloride, 0.46 g of potassium iodide, 6.5 g of anhydrous powdered potassium carbonate and 30 ml of acetonitrile was stirred and refluxed for 30 hours. Reaction monitoring by HPLC analysis indicated in situ formation of risperidone. After the completion of reaction, the reaction mixture was cooled and water (120 ml) was added under stirring. Separated solid stirred at [5°C] for [1] hour, filtered, washed with water and crystallized from ethyl acetate yielding 6 g [(81percent) OF 3- [2- [4- (6-FLUORO-L,] 2-benzisoxazole-3-yl) piperidino] [ETHYL-6,] 7,8, 9- [TETRAHYDRO-2-METHYL-4H-PYRIDO [1,] 2-a] pyrimidin-4-one. Example-5 A mixture of 4.75 g of [3- (2-CHLOROETHYL)-6,] 7,8, 9-tetrahydro-2-methyl-4H-pyrido [[1,] 2-a] [PYRIMIDIN-4-ONE,] 6.0 g [OF 4- (2,] 4-difluorobenzoyl) piperidine oxime hydrochloride, [0.] 46 g of potassium iodide, 6.1 g of anhydrous powdered potassium carbonate and 40 ml of acetonitrile was stirred and refluxed for 30 hours. The reaction mixture was cooled and water (120 [ML)] was added under stirring. Separated solid stirred at [5°C] for 1 hour, filtered, washed with water. Crude product was purified by crystallization in ethyl acetate to afford 6. [8] g (79percent) of [3- [2- [4- (6-FLUORO-1, 2-BENZISOXAZOLE-3-YL) PIPERIDINO] ETHYL]-6,] 7,8, 9-tetrahydro-2- methyl-4H-pyrido [1, 2-a] [PYRIMIDIN-4-ONE.]
77%	With potassium carbonate In DMF (N,N-dimethyl-formamide) at 95 - 100℃; for 18 h;	A mixture of 4.75 g of [3.] [(2-CHLOROETHYL)-6,] 7,8, 9-tetrahydro-2-methyl-4H-pyrido [[1,] 2-a] [PYRIMIDIN-4-ONE] hydrochloride, [5.] [1] g of 4- (2, 4-difluorobenzoyl) piperidine oxime hydrochloride, 0.46 g of potassium iodide, 6.5 g of anhydrous powdered potassium carbonate and 30 ml [OF N, N-DIMETHYLFORMAMIDE] was stirred at [95-100°C] for 18 hours. The reaction mixture was cooled and water (120 [ML)] was added under stirring. Separated solid stirred at [5°C] for 1 hour, filtered, washed with. water and crystallized from ethyl acetate yielding 5.7 g [(77percent)] of [3- [2- [4- (6-FLUORO-1,] 2-benzisoxazole-3-yl) piperidino] ethyl]-6, 7,8, 9-tetrahydro-2- [METHYL-4H-PYRIDO [1, 2-A] PYRIMIDIN-4-ONE.]

73%

With potassium carbonate In 4-methyl-2-pentanone at 100 - 105℃; for 30 h;

A mixture of 4.75 g of [3- (2-CHLOROETHYL)-6,] 7,8, [9-TETRAHYDRO-2-METHYL-4H-PYRIDO] [[1,] 2-a] pyrimidin-4-one hydrochloride, 5.1 g of 4-(2, 4-difluorobenzoyl) piperidine oxime hydrochloride, 0.46 g of potassium iodide, 6.5 g of anhydrous powdered potassium carbonate and 30 ml [OF MIBK] was stirred at [100105°C] for 30 hours. The reaction mixture was cooled and water (150 ml) was added under stirring. Separated solid stirred at [5°C] for 1 hour, filtered, washed with water and crystallized from ethyl acetate yielding 5.4 g (73percent) of [3- [2- [4- (6-FLUORO-1, 2-BENZISOXAZOLE-3-YL) PIPERIDINO] ETHYL]-6,] 7,8, 9-tetrahydro-2-methyl-4H- [PYRIDO] [[1,] 2-a] [PYRIMIDIN-4-ONE.]

Reference： [1] Patent: WO2004/9591, 2004, A1, . Location in patent: Page 7
[2] Patent: WO2004/9591, 2004, A1, . Location in patent: Page 5-6; 7
[3] Patent: WO2004/9591, 2004, A1, . Location in patent: Page 6
[4] Patent: WO2004/9591, 2004, A1, . Location in patent: Page 6

2
[ 135634-18-3 ]
[ 84163-77-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	for 4 h; Reflux	4) Preparation of 4-(6-fluoro-1,2-benzisoxazolyl)-piperidine 2,4-difluorophenyl-(4-piperidinyl)-methanone oxime hydrochloride (5.52g,20 mmol ) is added to 25 ml of 50 percent potassium hydroxide; reflux for 4 hours, cooled to room temperature, and extracted with toluene (25 mlx2). The combined organic phases are dried over anhydrous magnesium sulfate, filtered, evaporated to dryness under reduced pressure, and recrystallized in diethyl ether, to obtain 3.3g of a product, with a yield of 75 percent.
75%	With potassium hydroxide In toluene for 4 h; Reflux	2,4-difluorophenyl-(4-piperidinyl)methanone oxime hydrochloride (5.52 g, 20 mmol)Was added to 25 ml of 50percent potassium hydroxide, refluxed for 4 hours, cooled to room temperature, extracted with toluene 25 ml * 2, the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, Evaporate to dryness and recrystallize from diethyl ether to give 3.3 g of product. Yield is 75percent.

Reference： [1] Patent: EP2322520, 2011, A1, . Location in patent: Page/Page column 16
[2] Patent: JP5714152, 2015, B2, . Location in patent: Paragraph 0089

3
[ 135634-18-3 ]
[ 84163-13-3 ]

Yield	Reaction Conditions	Operation in experiment
35 g	Stage #1: With potassium hydroxide In methanol for 2.5 h; Heating Stage #2: With hydrogenchloride In water; acetone at 20℃; for 0 h;	Potassium hydroxide (27 g) was added to 600 mL of methanol and added(2,4-difluorophenyl) - (4-piperidinyl) methanone oxime hydrochloride (55 g)Heating reaction for about 2.5 hours. Cold to room temperature, add appropriate amount of anhydrous MgSO4, stirring about 1h. The filtrate was concentrated under reduced pressure. Join500 mL of acetone, stirred at room temperature for about 0.5 h, filtered, the filtrate stirred into the hydrochloric acid to pH = 2 ~ 3, filter, dry, white solidBody 35g. The methanol content is 0.4percent.

Reference： [1] Patent: CN106831742, 2017, A, . Location in patent: Paragraph 0041; 0042

4
[ 498-94-2 ]
[ 75-34-3 ]
[ 372-18-9 ]
[ 100-36-7 ]
[ 84162-82-3 ]
[ 135634-18-3 ]

Reference： [1] Patent: US5100902, 1992, A,

5
[ 59084-16-1 ]
[ 135634-18-3 ]

Reference： [1] Patent: EP2322520, 2011, A1,

6
[ 372-18-9 ]
[ 135634-18-3 ]

Reference： [1] Patent: EP2322520, 2011, A1,

7
[ 84162-82-3 ]
[ 135634-18-3 ]

Reference： [1] Patent: EP2322520, 2011, A1,

[ 135634-18-3 ] Synthesis Path-Downstream 1~18

1
3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride [ No CAS ]
[ 135634-18-3 ]
[ 106266-06-2 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium carbonate;potassium iodide; In acetonitrile; for 32h;Heating / reflux;	A mixture of 4.75 g of 3- (2-chloroethyl)-6, 7,8, 9-tetrahydro-2-methyl-4H-pyrido [[1,] [2-A] PYRIMIDIN-4-ONE] hydrochloride, 5.1 g of [4- (2,] 4-difluorobenzoyl) piperidine oxime hydrochloride, 0.46 g of potassium iodide, 5 g of anhydrous sodium carbonate and 30 ml of acetonitrile was stirred and refluxed for 32 hours. The reaction mixture was cooled and water (120 ml) was added under stirring. Separated solid stirred at [5 FOR 1] hour, filtered, washed with water and crystallized from ethyl acetate yielding 6 g (81%) of [3- [2- [4- (6-FLUORO-] [1,] [2-BENZISOXAZOLE-3-YL) PIPERIDINO] ETHYL]-6,] 7,8, [9-TETRAHYDRO-2-METHYL-4H-PYRIDO [ 1,] 2-a] [PYRIMIDIN-4-ONE.]
79 - 81%	With potassium carbonate;potassium iodide; In acetonitrile; for 30h;Heating / reflux;	A mixture of 4.75 g of [3-(2-CHLOROETHYL)-6,] 7,8, 9-tetrahydro-2-methyl-4H-pyrido [1, 2-a] pyrimidin-4-one hydrochloride, 5. 1 g of [4- (2, 4-DIFLUOROBENZOYL)] piperidine oxime hydrochloride, 0.46 g of potassium iodide, 6.5 g of anhydrous powdered potassium carbonate and 30 ml of acetonitrile was stirred and refluxed for 30 hours. Reaction monitoring by HPLC analysis indicated in situ formation of risperidone. After the completion of reaction, the reaction mixture was cooled and water (120 ml) was added under stirring. Separated solid stirred at [5C] for [1] hour, filtered, washed with water and crystallized from ethyl acetate yielding 6 g [(81%) OF 3- [2- [4- (6-FLUORO-L,] 2-benzisoxazole-3-yl) piperidino] [ETHYL-6,] 7,8, 9- [TETRAHYDRO-2-METHYL-4H-PYRIDO [1,] 2-a] pyrimidin-4-one. Example-5 A mixture of 4.75 g of [3- (2-CHLOROETHYL)-6,] 7,8, 9-tetrahydro-2-methyl-4H-pyrido [[1,] 2-a] [PYRIMIDIN-4-ONE,] 6.0 g [OF 4- (2,] 4-difluorobenzoyl) piperidine oxime hydrochloride, [0.] 46 g of potassium iodide, 6.1 g of anhydrous powdered potassium carbonate and 40 ml of acetonitrile was stirred and refluxed for 30 hours. The reaction mixture was cooled and water (120 [ML)] was added under stirring. Separated solid stirred at [5C] for 1 hour, filtered, washed with water. Crude product was purified by crystallization in ethyl acetate to afford 6. [8] g (79%) of [3- [2- [4- (6-FLUORO-1, 2-BENZISOXAZOLE-3-YL) PIPERIDINO] ETHYL]-6,] 7,8, 9-tetrahydro-2- methyl-4H-pyrido [1, 2-a] [PYRIMIDIN-4-ONE.]
77%	With potassium carbonate;potassium iodide; In DMF (N,N-dimethyl-formamide); at 95 - 100℃; for 18h;	A mixture of 4.75 g of [3.] [(2-CHLOROETHYL)-6,] 7,8, 9-tetrahydro-2-methyl-4H-pyrido [[1,] 2-a] [PYRIMIDIN-4-ONE] hydrochloride, [5.] [1] g of 4- (2, 4-difluorobenzoyl) piperidine oxime hydrochloride, 0.46 g of potassium iodide, 6.5 g of anhydrous powdered potassium carbonate and 30 ml [OF N, N-DIMETHYLFORMAMIDE] was stirred at [95-100C] for 18 hours. The reaction mixture was cooled and water (120 [ML)] was added under stirring. Separated solid stirred at [5C] for 1 hour, filtered, washed with. water and crystallized from ethyl acetate yielding 5.7 g [(77%)] of [3- [2- [4- (6-FLUORO-1,] 2-benzisoxazole-3-yl) piperidino] ethyl]-6, 7,8, 9-tetrahydro-2- [METHYL-4H-PYRIDO [1, 2-A] PYRIMIDIN-4-ONE.]

73%

With potassium carbonate;potassium iodide; In 4-methyl-2-pentanone; at 100 - 105℃; for 30h;

A mixture of 4.75 g of [3- (2-CHLOROETHYL)-6,] 7,8, [9-TETRAHYDRO-2-METHYL-4H-PYRIDO] [[1,] 2-a] pyrimidin-4-one hydrochloride, 5.1 g of 4-(2, 4-difluorobenzoyl) piperidine oxime hydrochloride, 0.46 g of potassium iodide, 6.5 g of anhydrous powdered potassium carbonate and 30 ml [OF MIBK] was stirred at [100105C] for 30 hours. The reaction mixture was cooled and water (150 ml) was added under stirring. Separated solid stirred at [5C] for 1 hour, filtered, washed with water and crystallized from ethyl acetate yielding 5.4 g (73%) of [3- [2- [4- (6-FLUORO-1, 2-BENZISOXAZOLE-3-YL) PIPERIDINO] ETHYL]-6,] 7,8, 9-tetrahydro-2-methyl-4H- [PYRIDO] [[1,] 2-a] [PYRIMIDIN-4-ONE.]

Reference： [1]Patent: WO2004/9591,2004,A1 .Location in patent: Page 7
[2]Patent: WO2004/9591,2004,A1 .Location in patent: Page 5-6; 7
[3]Patent: WO2004/9591,2004,A1 .Location in patent: Page 6
[4]Patent: WO2004/9591,2004,A1 .Location in patent: Page 6

2
3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride [ No CAS ]
[ 135634-18-3 ]
[ 158697-66-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;potassium iodide; In acetonitrile; for 30h;Heating / reflux;	A mixture of 5.58 g of [3- (2-CHLOROETHYL)-6,] 7,8, [9-TETRAHYDRO-2-METHYL-4H-PYRIDO] [1, 2-a] [PYRIMIDIN-4-ONE] hydrochloride, 5.1 g of 4- (2, 4-difluorobenzoyl) piperidine oxime hydrochloride, 0.46 g of potassium iodide, 6.76 g of anhydrous powdered potassium carbonate and 40 [ML] of acetonitrile was stirred and refluxed for 30 hours. Reaction monitoring by HPLC analysis indicated the formation of N-alkylated product, oxime, which subsequently [SLOWLY CYCLIZED IN SITU] to give risperidone. Thereafter, the reaction mixture was cooled and filtered. Residue was washed with cold water (50 [ML)] to remove the inorganics. Further washed with chilled ethyl acetate (5 [ML).] The product was crystallized from ethyl acetate yielding 6 g (81%) of [3- [2- [4- (6-FLUORO-1, 2-BENZISOXAZOLE-3-YL) PIPERIDINO] ETHYL]-] 6,7, 8, [9-TETRAHYDRO-2-METHYL-4H-PYRIDOF1, 2-A] PYRIMIDIN-4-ONE.]

Reference： [1]Patent: WO2004/9591,2004,A1 .Location in patent: Page 5

3
[ 498-94-2 ]
[ 75-34-3 ]
[ 372-18-9 ]
[ 100-36-7 ]
[ 84162-82-3 ]
[ 135634-18-3 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; hydroxylamine hydrochloride; acetic anhydride;aluminium trichloride; In hydrogenchloride; ethanol;	EXAMPLE 1 (RS)-3-[1-(benzocyclobuten-1-ylmethyl)-4-piperidyl]-6-fluoro-1,2-benzisoxazole hydriodide PROCESS No. 1 STAGE A: 1-Acetyl-4-piperidinecarboxylic acid 100 g of 4-piperidinecarboxylic acid and 400 ml of acetic anhydride are mixed. The mixture is brought to reflux for 2 hours and then left overnight at room temperature. The reaction medium is concentrated and the residue is ground with ethyl ether, filtered off and then washed with ethyl ether to obtain the expected compound. Yield: 79%. Melting point: 175 C. STAGE B: 1-Acetyl-4-piperidinecarbonyl chloride 52 g of the acid obtained in the preceding stage are added portionwise to 320 ml of thionyl chloride. After stirring overnight, the precipitate formed is filtered off and washed several times with isopropyl ether to isolate the expected product, which is used immediately without further purification. Yield: 80%. STAGE C: 1-Acetyl-4-(2,4-difluorobenzoyl)piperidine 54.3 g of aluminum chloride and 130 ml of dichloroethane are mixed. 24 g of 1,3-difluorobenzene are added and the acid chloride obtained in the preceding stage is then added portionwise. The reaction medium is brought to reflux for 6 hours and then left overnight at room temperature. It is hydrolyzed with ice and 190 ml of concentrated hydrochloric acid. The mixture is extracted 5 times with 100 ml of dichloromethane and the organic phase is dried over anhydrous magnesium sulfate to obtain the expected compound. Yield: 53%. Melting point: 97 C. STAGE D: 4-(2,4-Difluorobenzoyl)piperidine 30 g of 1-acetyl-4-(2,4-difluorobenzoyl)piperidine are brought to reflux in 113 ml of 6N hydrochloric acid for 6 hours. The reaction medium is then concentrated and the residue obtained is crystallized in isopropanol. The expected compound is isolated after filtration. Yield: 83%. Melting point: 230 C. STAGE E: 4-(2,4-Difluorobenzoyl)piperidine oxime hydrochloride 3 g of the compound obtained in the preceding stage, 3 g of hydroxylamine hydrochloride and 2.7 g of N,N-diethylethylenediamine are added to 30 ml of ethanol, and the mixture is brought to reflux for 8 hours. It is left overnight at room temperature and filtered and the residue isolated is rinsed with ethanol to obtain 4-(2,4-difluorobenzoyl)piperidine oxime hydrochloride. Yield: 54%. Melting point: >260 C. Proton nuclear magnetic resonance spectrum (solvent DMSO-d6): 1.7 ppm, m, 2H; 1.9 ppm, m, 2H; 2.70 ppm, m, 1H; 2.9 ppm, m, 2H; 3.25 ppm, m, 2H; 7.15 ppm, td, 1H; 7.3 ppm, m, 2H; 9.0 ppm, 1H exchangeable; 11.1 ppm, 1H exchangeable.

Reference： [1]Patent: US5100902,1992,A

4
(2,4-Difluoro-phenyl)-piperidin-4-yl-methanone hydrochloride [ No CAS ]
[ 135634-18-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With 2-(N,N-dimethylamino)athanol; hydroxylamine hydrochloride; In ethanol; at 20℃; for 3h;Reflux;	3) Preparation of 2,4-difluorophenyl-(4-piperidinyl)methanone oxime hydrochloride 2,4-difluorophenyl-(4-piperidine)methanone hydrochloride (3.0g, 11.5 mmol) and hydroxyamine hydrochloride (3.0g,42.8 mmol) are added to 5 ml of ethanol; thereto is drop-added 3 ml of N,N-dimethylethanolamine. The mixture is stirred at room temperature, refluxed for 3 hours, and then cooled to room temperature after completion of reaction. The deposit is filtered and dried to obtain 2.6g of the title compound as a white crystal product, with a yield of 96 %.
96%	With 2-(N,N-dimethylamino)athanol; hydroxylamine hydrochloride; In ethanol; at 20℃; for 3h;Reflux;	2,4-difluorophenyl(4-piperidinyl)methanone hydrochloride(3.0 g, 11.5 mmol) and hydroxylamine hydrochloride (3.0 g, 42.8 mmol) are added to 5 ml of ethanol. 3 ml of N,N-dimethylethanolamine is dropped into the solution, stirred at room temperature, and then refluxed for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, the precipitate was filtered and dried to obtain 2.6 g of the desired compound. This is a white crystalline material, and the yield is 96%.
55 g	With hydroxylamine hydrochloride; triethylamine; In ethanol; for 1h;Reflux;	70 g of 4- (2,4-difluorobenzoyl) piperidine hydrochloride was added to 840 mL of ethanol, and hydroxylamine hydrochloride70 g and 80 ml of triethylamine, heated to reflux for about 1 h. Cold to room temperature, filter, with a small amount of ethanol washing, drying, white solid55g.

Reference： [1]Patent: EP2322520,2011,A1 .Location in patent: Page/Page column 16
[2]Patent: JP5714152,2015,B2 .Location in patent: Paragraph 0088
[3]Patent: CN106831742,2017,A .Location in patent: Paragraph 0039; 0040

5
[ 59084-16-1 ]
[ 135634-18-3 ]