Synthesis
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Venlafaxine hydrochloride

Synthesis
Product Name
Venlafaxine hydrochloride
CAS No.
99300-78-4
Chemical Name
Venlafaxine hydrochloride
Synonyms
VENLAFAXINE HCL;EFFEXOR;D,L-VENLAFAXINE;D,L-VENLAFAXINE, HYDROCHLORIDE;Vexor;Venlift;AKOS 92111;VENLAFAXINEHCL;Venlaffaxine HCL;Venlafaxine HCL API
CBNumber
CB0136181
Molecular Formula
C17H28ClNO2
Formula Weight
313.86
MOL File
99300-78-4.mol
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Venlafaxine hydrochloride Property

Melting point:
207-209°C
Flash point:
9℃
storage temp. 
2-8°C
solubility 
H2O: >10mg/mL
form 
powder
color 
white
Merck 
14,9946
BCS Class
1
InChIKey
QYRYFNHXARDNFZ-UHFFFAOYSA-N
CAS DataBase Reference
99300-78-4(CAS DataBase Reference)
EPA Substance Registry System
Cyclohexanol, 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]-, hydrochloride (1:1 (99300-78-4)
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Safety

Hazard Codes 
Xi,T,F
Risk Statements 
36/37/38-36-39/23/24/25-23/24/25-11
Safety Statements 
26-37/39-45-36/37-16-7
RIDADR 
UN1230 - class 3 - PG 2 - Methanol, solution
WGK Germany 
3
RTECS 
GV8872760
HS Code 
29225090
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Danger
Hazard statements

H411Toxic to aquatic life with long lasting effects

Precautionary statements

P273Avoid release to the environment.

P391Collect spillage. Hazardous to the aquatic environment

P501Dispose of contents/container to..…

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N-Bromosuccinimide Price

Sigma-Aldrich
Product number
V-004
Product name
Venlafaxine hydrochloride solution
Purity
1.0?mg/mL in methanol (as free base), ampule of 1?mL, certified reference material, Cerilliant?
Packaging
1mL
Price
$99.4
Updated
2024/03/01
Sigma-Aldrich
Product number
PHR1736
Product name
Venlafaxine hydrochloride
Purity
Pharmaceutical Secondary Standard; Certified Reference Material
Packaging
1g
Price
$132
Updated
2024/03/01
Sigma-Aldrich
Product number
1711268
Product name
Venlafaxine hydrochloride
Purity
United States Pharmacopeia (USP) Reference Standard
Packaging
100mg
Price
$553
Updated
2024/03/01
TCI Chemical
Product number
V0110
Product name
Venlafaxine Hydrochloride
Purity
>98.0%(HPLC)(T)
Packaging
1g
Price
$86
Updated
2024/03/01
TCI Chemical
Product number
V0110
Product name
Venlafaxine Hydrochloride
Purity
>98.0%(HPLC)(T)
Packaging
5g
Price
$259
Updated
2024/03/01
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Venlafaxine hydrochloride Chemical Properties,Usage,Production

Synthesis

Venlafaxine (92.4 g) was dissolved in ethyl acetate (450 ml) at 50-55 ºC, filtered hot then cooled to 10-15 ºC and pH was adjusted to <2 with addition of isopropyl alcohol saturated with HCl gas and allowed to stand for 15 minutes. The white solid was filtered off, washed with EtOAc (75 ml), and then with petroleum ether (150 ml). The crystalline salt was dissolved in MeOH (160 ml) at 50-55 ºC and filtered when hot. The hydrochloride salt 35 was precipitated by adding ethyl acetate drop-wise, at room temperature. After 4 hours the solid was filtered and washed with ethyl acetate (100 ml). The solid (98.3 g) was allowed to dry in air (6-8 hours).

Description

Venlafaxine hydrochloride, a novel phenethylamine derivative, was introduced in the U.S.A. as an antidepressant. Venlafaxine is reported to be the first in the class of the second-generation of antidepressants with dual serotonidnorepinephrine reuptake inhibitory activity. Venlafaxine lacks any affinity for muscarinic, cholinergic, histaminergic and noradrenergic receptors and therefore, has an unusually favorable side effect profile compared with classical tricyclic antidepressants and shows less cardiotoxicity. In addition, venlafaxine has a rapid onset of action that makes it unique among the antidepressant agents. Other indications for venlafaxine include the treatment of obsessive and panic disorders, and obesity. Both enantiomers of venlafaxine were reported to have similar biological activity.

Chemical Properties

White Crystalline Powder

Originator

Wyeth-Ayerst (U.S.A.)

Uses

A selective serotonin noradrenaline reuptake inhibitor. Used as an antidepressant

Uses

An inhibitor of ST and SLC6A2.

Uses

Venlafaxine hydrochloride is an inhibitor of reuptake of both serotonin (IC50 = 0.21 μM) and norepinephrine (IC50 = 0.64 μM). It is effective in vitro and in vivo and against human as well as rat receptors. As an antidepressant, it is properly placed in the serotonin-norepinephrine reuptake inhibitor class.[Cayman Chemical]

Manufacturing Process

1-[Cyano(-methoxyphenyl)methyl]cyclohexanol
p-Methoxyphenylacetonitrile (50 gm, 0.3 mole) was added to dry tetrahydrofuran (250 ml) and the solution cooled to -70°C under nitrogen. n- Butyl lithium in hexane (210 ml, 0.3 mole) was added dropwise, with stirring. The temperature was maintained below -50°C and a yellow precipitate appeared. After the addition was complete, the reaction mixture was maintained below -50°C for 30 minutes and cyclohexanone (35 ml, 0.3 mole)was added. After a further 45 minutes below -50°C the temperature was allowed to rise to 0°C and a saturated ammonium chloride solution was added. The layers were separated and the aqueous layer extracted with diethyl ether. The combined organic solution was washed with brine, dried over magnesium sulfate and evaporated. The product crystallized (25.2 gm, melting point 125°-127°C). The structure was confirmed by N.M.R. and mass spectral analysis.
1-[2-Amino-1-(p-methoxyphenyl)ethyl]cyclohexanol
1-[Cyano(p-methoxyphenyl)methyl]cyclohexanol (12 g, 0.05 mole) was dissolved on warming in a mixture of ammonia-ethanol (20% v/v, 250 ml) and hydrogenated in a Parr apparatus over 5% rhodium an alumina (2.8 gm). The catalyst was filtered, washed well with ethanol and the combined filtrate evaporated and dried under vacuum yielding an oil (12 gm). Thin layer chromatography: single spot, ninhydrin positive [chloroform-methanol-acetic acid (80:10:10 v/v)].
1-[-2-Dimethyl-amino)-1-(4-methoxyphenyl)-ethyl]cyclohexanol
1-[2-Amino-1-(p-methoxyphenyl)ethyl]cyclohexanol (12 gm; 0.048 mole) was treated with a mixture of formaldehyde (11 ml), formic acid (14.5 ml, 88%) and water (125 ml) and heated at 100°C for five hours. The reaction mixture was cooled and extracted with ethyl acetate. This extract was discarded. The aqueous residue was cooled in ice, rendered basic by the addition of solid potassium hydroxide, saturated with sodium chloride and extracted 3 times with ethyl acetate. The extract was washed with brine, dried over anhydrous potassium carbonate and evaporated to an oily residue (8 gm). This mixture of products was chromatographed on 1 kg of Mallinckrodt Silicar CC7 silica gel and the progress of the chromatography was monitored by thin layer chromatrography using a system comprising ethanol:2 N ammonia:ethyl acetate:cyclohexane 45:8:100:100 (v/v). Fractions containing the desired product were combined and the hydrochloride salt prepared using 4 N HCl in isopropanol. The yield of the free base was 4.6 gm of 1-[(2-dimethylamino)- 1-(4-methoxyphenyl)ethyl]-cyclohexanol. The hydrochloride (venlafaxine): melting point 215°-217°C. The structure was confirmed by mass spectral analysis and N.M.R. analysis.

brand name

Effexor (Wyeth).

Therapeutic Function

Antidepressant

General Description

A Certified Snap-N-Spike? Solution suitable for many LC/MS and GC/MS applications from forensic or clinical toxicology analysis to urine drug testing. Also known by the brand name Effexor?, venlafaxine is an SNRI antidepressant approved for the treatment of major depressive and general anxiety disorders.

Biological Activity

Dual serotonin/noradrenalin re-uptake inhibitor that displays ~ 30-fold higher affinity for SERT than NET (K i values are 82 and 2480 nM respectively). Antidepressant; increases swimming and climbing behavior in the forced-swim test in rats.

Biochem/physiol Actions

Venlafaxine is an antidepressant. The mechanism of the antidepresant action of venlafaxine in humans is associated with its potentiation of neurotransmitter activity in the CNS. Venlafaxine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and weak inhibitor of dopamine reuptake. Venlafaxine has no significant activity for muscarinic, histaminergic, or α-1 adrenergic receptors in vitro. Venlafaxine does not possess MAO inhibitor activity.

storage

Store at RT

Venlafaxine hydrochloride Preparation Products And Raw materials

Raw materials

Preparation Products

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Venlafaxine hydrochloride Suppliers

Zhejiang Jiuzhou Pharmaceutical Co., Ltd
Tel
13566413511
Email
le.sun@jiuzhoupharma.com
Country
China
ProdList
31
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58
Hunan Revel Biotechnology Co. , Ltd.
Tel
19359985961 19359985961
Email
2430503320@qq.com
Country
China
ProdList
1469
Advantage
58
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
94657
Advantage
76
Meryer (Shanghai) Chemical Technology Co., Ltd.
Tel
021-61259108 18621169109
Fax
86-21-61259102
Email
market03@meryer.com
Country
China
ProdList
40228
Advantage
62
INTATRADE GmbH
Tel
+49 3493/605464
Fax
+49 3493/605470
Email
sales@intatrade.de
Country
Germany
ProdList
3572
Advantage
66
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel
821-50328103-801 18930552037
Fax
86-21-50328109
Email
3bsc@sina.com
Country
China
ProdList
15839
Advantage
69
TAIYUAN RHF CO.,LTD.
Tel
+86 351 7031519
Fax
+86 351 7031519
Email
sales@RHFChem.com
Country
China
ProdList
2338
Advantage
56
TCI (Shanghai) Development Co., Ltd.
Tel
021-67121386
Fax
021-67121385
Email
Sales-CN@TCIchemicals.com
Country
China
ProdList
24529
Advantage
81
Beijing HwrkChemical Technology Co., Ltd
Tel
010-89508211 18501085097
Fax
010-89508210
Email
sales.bj@hwrkchemical.com
Country
China
ProdList
8418
Advantage
55
Energy Chemical
Tel
021-021-58432009 400-005-6266
Fax
021-58436166
Email
sales8178@energy-chemical.com
Country
China
ProdList
44688
Advantage
61
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View Lastest Price from Venlafaxine hydrochloride manufacturers

Hebei Weibang Biotechnology Co., Ltd
Product
Venlafaxine HCl 99300-78-4
Price
US $9.90/KG
Min. Order
1KG
Purity
99%
Supply Ability
10 mt
Release date
2024-11-21
BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.
Product
Venlafaxine Hydrochloride 99300-78-4
Price
US $0.00/g
Min. Order
1g
Purity
More Than 99%
Supply Ability
100kg/Month
Release date
2024-09-05
Hebei Yanxi Chemical Co., Ltd.
Product
Venlafaxine hydrochloride 99300-78-4
Price
US $50.00/kg
Min. Order
1kg
Purity
0.99
Supply Ability
100000
Release date
2023-09-12

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