5570-77-4

Basic information

• Product Name: 4-Chloro-N-methylpiperidine
• Synonyms: 4-chloro-1-methyl-piperidin;4-CHLORO-N-METHYL PIPERIDINE;4-CHLORO-1-METHYLPIPERIDINE;1-METHYL-4-CHLORO-PIPERIDINE;N-METHYL-4-CHLORO PIPERIDINE;N- METHYL 4 CHLORO PIPERIDINE BASE;N-Methyl-4-Chloropiperdine/4-Chloro-1-Methylpiperidine;N-Methyl-4-chloro
• CAS NO: 5570-77-4
• Molecular Formula: C₆H₁₂ClN
• Molecular Weight: 133.62
• EINECS: 226-942-4
• Product Categories: PHARMACEUTICAL INTERMEDIATES;Heterocyclic Compounds
• Mol File: 5570-77-4.mol
• Article Data: 8

Chemical Properties

• Melting Point: 160-165°C
• Boiling Point: 162°C(lit.)
• Flash Point: 48 °C
• Appearance: /
• Density: 1.02
• Vapor Pressure: 0.293mmHg at 25°C
• Refractive Index: 1.4670-1.4710
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 7.88±0.10(Predicted)
• Water Solubility: 1.533g/L at 29℃
• CAS DataBase Reference: 4-Chloro-N-methylpiperidine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-N-methylpiperidine(5570-77-4)
• EPA Substance Registry System: 4-Chloro-N-methylpiperidine(5570-77-4)

Safety Data

• Hazard Codes: Xi,C
• Statements: 10-34-36/38
• Safety Statements: 22-24/25-45-36/37/39-26-36-16
• RIDADR: 1993
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 5570-77-4(Hazardous Substances Data)

Usage

Chemical Properties

Clear colorless liquid

Flammability and Explosibility

Notclassified

InChI:InChI=1/C5H11ClN2/c6-5-1-3-8(7)4-2-5/h5H,1-4,7H2

Synthetic route

N-methyl-4-hydroxypiperidine (106-52-5) → 4-chloro-1-methylpiperidine (5570-77-4)

Conditions	Yield
With thionyl chloride; triethylamine In dichloromethane at 20 - 40℃; for 2h;	80%
With thionyl chloride; benzene
With thionyl chloride

1-methylpiperidin-2-one (931-20-4) + 4-chloromethyl-1-tritylimidazole (103057-10-9) → 4-chloro-1-methylpiperidine (5570-77-4)

Conditions	Yield
With n-butyllithium; ammonia; diisopropylamine In tetrahydrofuran; methanol; dichloromethane; water; ethyl acetate	52%
With n-butyllithium; ammonia; diisopropylamine In tetrahydrofuran; methanol; dichloromethane; water; ethyl acetate	52%

1-Methyl-4-piperidone (1445-73-4) → 4-chloro-1-methylpiperidine (5570-77-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Raney nickel / 125 °C / 102971 Torr / Hydrogenation 2: benzene; thionyl chloride View Scheme

ethyl 1-methyl-4-oxo-piperidin-3-carboxylate (25012-72-0) → 4-chloro-1-methylpiperidine (5570-77-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: water; hydrochloric acid 2: Raney nickel / 125 °C / 102971 Torr / Hydrogenation 3: benzene; thionyl chloride View Scheme

3,3'-methylimino-di-propionic acid diethyl ester (6315-60-2) → 4-chloro-1-methylpiperidine (5570-77-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaH; benzene 2: water; hydrochloric acid 3: Raney nickel / 125 °C / 102971 Torr / Hydrogenation 4: benzene; thionyl chloride View Scheme

4-chloro-N-methyl-piperidine hydrochloride (5382-23-0) → 4-chloro-1-methylpiperidine (5570-77-4)

Conditions	Yield
With potassium hydroxide
With ammonia
With potassium carbonate In water	14 g

4-chloro-1-methylpiperidine (5570-77-4) + dibenzosuberenon (2222-33-5) → 5-(1-methyl-4-piperidyl)-5H-dibenzocyclohepten-5-ol (3967-32-6)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 5h; Reflux; Inert atmosphere; Stage #2: With (trimethylsilyl)methylmagnesium chloride; lithium chloride; zinc(II) chloride In tetrahydrofuran; diethyl ether at 20℃; for 0.75h; Inert atmosphere; Stage #3: dibenzosuberenon In tetrahydrofuran; diethyl ether at 0℃; for 2h; Inert atmosphere;	99%
Stage #1: 4-chloro-1-methylpiperidine With magnesium In tetrahydrofuran at 60 - 65℃; for 1h; Inert atmosphere; Large scale; Stage #2: dibenzosuberenon In tetrahydrofuran at 5 - 20℃; for 1h; Temperature; Inert atmosphere; Large scale;

4-chloro-1-methylpiperidine (5570-77-4) + 2-Thiobarbituric acid (91759-32-9) → 2-<(1-Methylpiperidin-4-yl)sulfanyl>pyrimidine-4,6-diol hydrochloride

Conditions	Yield
In acetone for 1h; Ambient temperature;	94%

4-chloro-1-methylpiperidine (5570-77-4) → 4-chloro-1-formylpiperidine

Conditions	Yield
With [2,2]bipyridinyl; C10H16NO; copper(II) bis(trifluoromethanesulfonate); copper(l) chloride In acetonitrile at 20℃; for 2h;	91%

4-chloro-1-methylpiperidine (5570-77-4) + C15H15N3O2 (957199-68-7) → 1-[2-(dimethylamino)ethyl]-4-hydroxy-4-(1-methylpiperidin-4-yl)-1H-pyrrolo[3,2-g]isoquinolin-9(4H)-one (1182125-60-5)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With magnesium In tetrahydrofuran for 1h; Inert atmosphere; Reflux; Stage #2: C15H15N3O2 In tetrahydrofuran at 0℃; Inert atmosphere; Reflux;	85%

4-chloro-1-methylpiperidine (5570-77-4) + 3-[2-(3-chlorophenyl)ethyl]-2-pyridine-carbonitrile (31255-57-9) → 1-(METHYL-4-PIPERIDINYL)[3-(2-(3-CHLORO-PHENYL)ETHYL)-2-PYRIDINYL]METHANONE HYDROCHLORIDE (119770-60-4)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran; ethylene dibromide at 75℃; for 1h; Inert atmosphere; Stage #2: 3-[2-(3-chlorophenyl)ethyl]-2-pyridine-carbonitrile In tetrahydrofuran; ethylene dibromide at 40 - 50℃; for 1h; Inert atmosphere; Stage #3: With hydrogenchloride; water In tetrahydrofuran; ethylene dibromide at 20℃; for 1h; pH=< 2; Inert atmosphere;	83.3%

4-chloro-1-methylpiperidine (5570-77-4) + benzaldehyde (100-52-7) → (1-methylpiperidin-4-yl)(phenyl)methanol (92196-29-7)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With magnesium; lithium chloride In tetrahydrofuran at 50℃; for 0.125h; Flow reactor; Stage #2: benzaldehyde In tetrahydrofuran at 20℃; for 0.333333h; Flow reactor;	81%

4-chloro-1-methylpiperidine (5570-77-4) + 8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (31251-41-9) → 8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (38089-93-9)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With magnesium; ethylene dibromide In tetrahydrofuran at 20 - 48℃; Stage #2: 8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one In tetrahydrofuran at -80 - -70℃; for 2 - 3h; Product distribution / selectivity;	73.6%

4-chloro-1-methylpiperidine (5570-77-4) + ammonium chloride + 9-Fluoro-5,6-dihydro-(1H)-benzo[5,6]cyclohepta[1,2-b]-pyridin-11-one (111108-54-4) → 9-Fluoro-11-(1-Methyl-4-Piperidinyl)-6,11-Dihydro-5H-Benzo[5,6]Cyclohepta[1,2-b]Pyridin-11-Ol (111108-55-5)

Conditions	Yield
With magnesium In tetrahydrofuran; chloroform	70%

4-chloro-1-methylpiperidine (5570-77-4) + 9-Fluoro-5,6-dihydro-(1H)-benzo[5,6]cyclohepta[1,2-b]-pyridin-11-one (111108-54-4) → 9-Fluoro-11-(1-Methyl-4-Piperidinyl)-6,11-Dihydro-5H-Benzo[5,6]Cyclohepta[1,2-b]Pyridin-11-Ol (111108-55-5)

Conditions	Yield
In tetrahydrofuran; chloroform	70%

4-chloro-1-methylpiperidine (5570-77-4) + calcium carbide (75-20-7) → 4-chloro-1-(prop-2-yn-1-yl)piperidine

Conditions	Yield
With copper(I) bromide; diethylazodicarboxylate In water; acetonitrile at 90℃; for 16h; Inert atmosphere;	70%

4-chloro-1-methylpiperidine (5570-77-4) + 3-methoxy-5H-dibenzo[a,d]cyclohepten-5-one (22725-38-8) → 4-(3-methoxy-dibenzo[a,d]cyclohepten-5-ylidene)-1-methyl-piperidine (64618-74-2, 64618-76-4, 77263-46-8)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 1.5h; Inert atmosphere; Reflux; Stage #2: 3-methoxy-5H-dibenzo[a,d]cyclohepten-5-one In tetrahydrofuran at 20℃; Stage #3: for 3h; Reflux; Acidic conditions;	69%

4-chloro-1-methylpiperidine (5570-77-4) + chloro-bis(dimethylamino)borane (6562-41-0) + water (7732-18-5) → N-methylpiperidine-4-boronic acid

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine; chloro-bis(dimethylamino)borane With lithium In tetrahydrofuran at -5 - 5℃; for 1h; Inert atmosphere; Stage #2: water With hydrogenchloride In tetrahydrofuran at 0 - 20℃; pH=6;	66%

4-chloro-1-methylpiperidine (5570-77-4) + thiophenol (108-98-5) → 1-methyl-4-phenylsulfanylpiperidine (738568-03-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 72h; Ambient temperature;	64%

4-chloro-1-methylpiperidine (5570-77-4) + 3-[(3-Chlorophenyl)thiomethyl]-N-methoxy-N-methyl-2-pyridine-carboxamide (205984-57-2) + CeCl3/ THF → [3-[(3-chlorophenyl)thiomethyl]-2-pyridinyl][1-methyl-4-piperidinyl]methanone

Conditions	Yield
With N2; CeCl3 In tetrahydrofuran	64%

4-chloro-1-methylpiperidine (5570-77-4) + 3-[(3-Chlorophenyl)thiomethyl]-N-methoxy-N-methyl-2-pyridine-carboxamide (205984-57-2) + CeCl3/THF → [3-[(3-chlorophenyl)thiomethyl]-2-pyridinyl][1-methyl-4-piperidinyl]methanone

Conditions	Yield
With N2; CeCl3 In tetrahydrofuran	64%

4-chloro-1-methylpiperidine (5570-77-4) + 2-bromo-5H-dibenzo[a,d][7]annulen-5-one (124853-22-1) → 2-bromocyproheptadine

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 1.5h; Inert atmosphere; Reflux; Stage #2: 2-bromo-5H-dibenzo[a,d][7]annulen-5-one In tetrahydrofuran at 20℃; Stage #3: for 3h; Reflux; Acidic conditions;	63%

4-chloro-1-methylpiperidine (5570-77-4) + 4-Fluorothiophenol (371-42-6) → 4-(4-fluoro-phenylsulfanyl)-1-methyl-piperidine (66496-80-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide for 72h; Ambient temperature;	61%

4-chloro-1-methylpiperidine (5570-77-4) + 2-methoxy-5H-dibenzo[a,d]cyclohepten-5-one (42982-04-7) → C22H23NO

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 1.5h; Inert atmosphere; Reflux; Stage #2: 2-methoxy-5H-dibenzo[a,d]cyclohepten-5-one In tetrahydrofuran at 20℃; Stage #3: for 3h; Reflux; Acidic conditions;	60%

4-chloro-1-methylpiperidine (5570-77-4) + 2-chloro-10,11-dihydrodibenzothiepin-10-thiol (133242-15-6) → 4-(2-chloro-10,11-dihydrodibenzothiepin-10-ylthio)-1-methylpiperidine (134615-47-7)

Conditions	Yield
With sodium ethanolate In N,N-dimethyl-formamide at 90℃; for 3.5h;	55%

4-chloro-1-methylpiperidine (5570-77-4) + 2-chloro-7-methoxy-dibenzo[a,d]cyclohepten-5-one (1221486-44-7) → C22H22ClNO

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 1.5h; Inert atmosphere; Reflux; Stage #2: 2-chloro-7-methoxy-dibenzo[a,d]cyclohepten-5-one In tetrahydrofuran at 20℃; Stage #3: for 3h; Reflux; Acidic conditions;	54%

4-chloro-1-methylpiperidine (5570-77-4) + C16H11BrO2 → C22H22BrNO

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 1.5h; Inert atmosphere; Reflux; Stage #2: C16H11BrO2 In tetrahydrofuran at 20℃; Stage #3: for 3h; Reflux; Acidic conditions;	54%

4-chloro-1-methylpiperidine (5570-77-4) + C16H11BrO2 → C22H22BrNO

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 1.5h; Inert atmosphere; Reflux; Stage #2: C16H11BrO2 In tetrahydrofuran at 20℃; Stage #3: for 3h; Reflux; Acidic conditions;	54%

4-chloro-1-methylpiperidine (5570-77-4) + 2-fluoro-5-iodobenzoyl chloride (186584-73-6) → 4-(2-fluoro-5-iodobenzoyl)-1-methylpiperidine (952305-12-3)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With magnesium In tetrahydrofuran Stage #2: 2-fluoro-5-iodobenzoyl chloride In tetrahydrofuran at -78 - 0℃;	53%

4-chloro-1-methylpiperidine (5570-77-4) + 2-fluorobenzonitrile (394-47-8) → (RS)-3-[1-(Benzocyclobuten-1-ylmethyl)-4-piperidyl]-1,2-benzisoxazole hydrochloride

Conditions	Yield
With ammonium chloride In tetrahydrofuran; water	50%

4-chloro-1-methylpiperidine (5570-77-4) + 2-hydroxy-11-oxo-6,11-dihydrodibenz[b,e]oxepine (50456-78-5) → 11-(1-Methylpiperidin-4-yl)-6,11-dihydrodibenzo[b,e]oxepine-2,11-diol (872041-17-3)

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 12 - 24h; Heating / reflux; Stage #2: 2-hydroxy-11-oxo-6,11-dihydrodibenz[b,e]oxepine In tetrahydrofuran at 0℃; for 1h; Stage #3: With water; ammonium chloride In tetrahydrofuran	50%

4-chloro-1-methylpiperidine (5570-77-4) + 8-Cyano-5,6-dihydro-1H-benzo[5,6]cyclohepta[1.2-b]pyridin-11-one → 8-cyano-6,11-dihydro-11-(1-methyl-4-piperidyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol (143540-50-5)

Conditions	Yield
With ammonium chloride; magnesium	47%

4-chloro-1-methylpiperidine (5570-77-4) + 8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (31251-41-9) → 8-chloro-3-(1-methylpiperidin-4-yl)-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridine-11-one

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With magnesium; ethylene dibromide In tetrahydrofuran at 65℃; Stage #2: 8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one In tetrahydrofuran at 10℃; for 0.5h; Temperature;	44%
Stage #1: 4-chloro-1-methylpiperidine With N,N,N,N,-tetramethylethylenediamine; magnesium; ethylene dibromide In tetrahydrofuran at 65℃; Stage #2: 8-chloro-5,6-dihydro-11H-Benzo[5,6]cyclohepta[1,2-b]pyridin-11-one In tetrahydrofuran at 10℃; for 0.5h; Reagent/catalyst; Temperature;	44%

4-chloro-1-methylpiperidine (5570-77-4) + C16H11BrO2 → C22H22BrNO

Conditions	Yield
Stage #1: 4-chloro-1-methylpiperidine With iodine; magnesium In tetrahydrofuran for 1.5h; Inert atmosphere; Reflux; Stage #2: C16H11BrO2 In tetrahydrofuran at 20℃; Stage #3: for 3h; Reflux; Acidic conditions;	39%

Upstream product

• 931-20-4 1-methylpiperidin-2-one 
• 103057-10-9 4-chloromethyl-1-tritylimidazole 
• 5382-23-0 4-chloro-N-methyl-piperidine hydrochloride 
• 6315-60-2 3,3'-methylimino-di-propionic acid diethyl ester 
• 25012-72-0 ethyl 1-methyl-4-oxo-piperidin-3-carboxylate 
• 1445-73-4 1-Methyl-4-piperidone 
• 106-52-5 N-methyl-4-hydroxypiperidine 

Downstream Products

• 4945-47-5 bamipine 
• 102166-77-8 N-benzyl-N-(1-methyl-[4]piperidyl)-p-toluidine 
• 102009-35-8 N-(4-chloro-benzyl)-N-(1-methyl-[4]piperidyl)-aniline 
• 102166-98-3 N-(4-methoxy-benzyl)-N-(1-methyl-[4]piperidyl)-aniline 
• 66496-80-8 4-(4-fluoro-phenylsulfanyl)-1-methyl-piperidine 
• 738568-03-1 1-methyl-4-phenylsulfanylpiperidine 
• 135235-70-0 (2-fluorophenyl)[3-[(1-methyl-4-piperidinyl)hydroxymethyl]-thien-2-yl]methanone 
• 38089-93-9 8-chloro-6,11-dihydro-11-(1-methyl-4-piperidinyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol 
• 1241898-42-9 (2-bromo-5-fluorophenyl)(1-methylpiperidin-4-yl)methanone 
• 799828-29-8 (3-chlorophenyl)(1-methylpiperidin-4-yl)methanone 
• 799828-36-7 C₁₄H₁₉NO₂ 
• 105283-58-7 phenyl 4-chloro-1-piperidine-carboxylate 
• 117811-07-1 5-Methoxy-8-chloro-11-(1-methyl-4-piperidinyl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol 
• 110-89-4 piperidine 

Relevant articles and documents

Synthesis of 3H, 13C,2H3,15N and 14C-labelled SCH 466036, a histamine 3 receptor antagonist

The synthesis of [3H]SCH 466036, [Me-3H3]SCH 466036, [13C,2H3,15N]SCH 466036 and [14C]SCH 466036 is described. [3H]SCH 466036 was prepared in two steps via Raney Ni-catalysed exchange with tritiated water. [Me-3H3]SCH 466036 was prepared in a single step from [3H]methyl iodide in 45% yield. [13C,2H3,15N]SCH 466036 was prepared in two steps from [15N] hydroxylamine and [13C,2H3]methyl iodide with an overall yield of 16%. [14C]SCH 466036 was prepared in seven steps from [14C]potassium cyanide in an overall yield of 13%.

Process method for synthesizing N-substituted piperidine-4-boric acid

The invention relates to an organic compound synthesis method, and relates to a process method for synthesizing N-substituted piperidine-4-boric acid, which comprises the following steps of: reactingN-substituted piperidine-4-alcohol used as a raw material with thionyl chloride and organic alkali in a solvent to generate N-substituted piperidine-4-chlorine, reacting the N-substituted piperidine-4-chlorine used as a raw material with lithium metal and bis (N, N-dimethylamino) borane halide in a solvent, quenching and acidifying to obtain N-substituted piperidine-4-boric acid. The process method has the advantages of originality, low cost, safety and mild reaction conditions, avoids the dangerous reaction that other patented methods adopt expensive palladium hydroxide hydrogenation, has potential cost advantage and safety advantage, and is suitable for industrial scale-up production.

DIHYDROBENZOTHIOPHENES

The invention relates to compounds of formula (I), in which W, R1, R2, R3, R4, and q are defined as cited in claim 1. One application for said compounds is the treatment of tumours.