99300-78-4 Usage
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
Different sources of media describe the Uses of 99300-78-4 differently. You can refer to the following data:
1. A selective serotonin noradrenaline reuptake inhibitor. Used as an antidepressant
2. 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]
3. An inhibitor of ST and SLC6A2.
Manufacturing Process
1-[Cyano(-methoxyphenyl)methyl]cyclohexanolp-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]cyclohexanol1-[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]cyclohexanol1-[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.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 99300-78-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 9,9,3,0 and 0 respectively; the second part has 2 digits, 7 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 99300-78:
(7*9)+(6*9)+(5*3)+(4*0)+(3*0)+(2*7)+(1*8)=154
154 % 10 = 4
So 99300-78-4 is a valid CAS Registry Number.
InChI:InChI=1/C17H27NO2.ClH/c1-18(2)13-16(17(19)11-5-4-6-12-17)14-7-9-15(20-3)10-8-14;/h7-10,16,19H,4-6,11-13H2,1-3H3;1H
99300-78-4Relevant articles and documents
Method for industrially producing venlafaxine hydrochloride
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Paragraph 0083-0090, (2021/09/26)
The invention discloses a method for industrially producing venlafaxine hydrochloride, and relates to the technical field of drug organic synthesis. The method has the advantages of easily available raw materials of the whole synthetic route, mild reaction conditions, simple and convenient operation, high yield, environment friendliness and good repeatability of the preparation method, and can be used for preparing venlafaxine hydrochloride with high yield and high purity.
A method for preparing venlafaxine hydrochloride (by machine translation)
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Paragraph 0036; 0038; 0039; 0041; 0042; 0044, (2019/04/10)
The invention provides a preparation method of venlafaxine hydrochloride, comprises the following steps: in the borohydride and of Lewis acids in reduction system under I compound formula II compound suitcase; the formula II compound acid formation to get to the venlafaxine hydrochloride; according to the present invention provides a preparation method of venlafaxine hydrochloride, the reaction process is safe, easy to control, and the cost is low, the ideal result, is suitable for industrial production. (by machine translation)
A 1 - [2-amino-1 - (4-methoxyphenyl) ethyl] cyclohexanol of the sulphate preparation method
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Paragraph 0031-0032, (2016/10/09)
The invention discloses a preparation method of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol sulfate. The method comprises the following steps: dissolving 1-cyano-[(4-methoxyphenyl)methyl]cyclohexanol in an organic solvent, and adding a Co-NiO dual catalyst at normal temperature; replacing air in the reactor with hydrogen gas, and reacting for 2-4 hours while controlling the pressure at 0.1-0.5 MPa and the temperature at 80-140 DEG C; after the reaction finishes, cooling the reaction solution to room temperature, filtering, and dropwisely adding concentrated hydrochloric acid into the filtrate; and after finishing the dropwise addition, cooling to 0-10 DEG C, keeping the temperature to crystallize, carrying out vacuum filtration and drying to obtain the 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol sulfate. By adopting the dual catalyst Co-NiO with high catalytic activity, the method shortens the reaction time, enhances the product yield, and has the advantage of simple after-treatment steps; and thus, the technique is easier for industrial production.
