CN109651094A - A kind of preparation method of p- (2- methoxyl group) ethyl -phenol - Google Patents
A kind of preparation method of p- (2- methoxyl group) ethyl -phenol Download PDFInfo
- Publication number
- CN109651094A CN109651094A CN201811635234.8A CN201811635234A CN109651094A CN 109651094 A CN109651094 A CN 109651094A CN 201811635234 A CN201811635234 A CN 201811635234A CN 109651094 A CN109651094 A CN 109651094A
- Authority
- CN
- China
- Prior art keywords
- phenol
- methoxyl group
- method described
- ethyl
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/05—Preparation of ethers by addition of compounds to unsaturated compounds
- C07C41/06—Preparation of ethers by addition of compounds to unsaturated compounds by addition of organic compounds only
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
Abstract
The present invention is etherified to react the parachlorophenol that phenolic hydroxyl group protection is made using parachlorophenol as raw material, then generates p- (2- methoxyl group) ethyl -phenol by grignard reaction, chloro, methoxy substitution reaction.The novel preparation method of p- (2- methoxyl group) ethyl -phenol of the present invention, raw material are easy to get, and reaction condition is mild, safety coefficient is high, and strong operability, simple process is easily industrialized, and product purity is high, and quality is stablized, and complies fully with the requirement as medicine intermediate.
Description
Technical field
The present invention relates to organic synthetic pharmacochemistry fields, more specifically, are related to a kind of metoprolol intermediate: p-
The novel preparation method of (2- methoxyl group) ethyl -phenol.
Background technique
P- (2- methoxyl group) ethyl -phenol is the key intermediate of synthetic drug metoprolol.Metoprolol
It (metoprolol) is a kind of aminopropanol class drug, selective β1receptorblocker is world's hypertension therapeutic in recent years
Drug of first choice.It and there is the adrenaline of excitation and norepinephrine to be at war with, and in the guarded by location heart of receptor
It is dirty, inhibit cardiac contractile force, avoid nerve impulse of being overexcited and prevent.Itself also ensures the contraction of heart wall smooth muscle.
And it also has good curative effect to the angina pectoris as caused by anoxic.
It mainly includes following several that p- (2- methoxyl group) ethyl -phenol synthesis, which sums up:
Synthetic route 1:
The route is from para-nitrotoluene, by condensation, methyl-etherified, reduction, p- (the 2- methoxy of diazotising hydrolysis
Base) ethyl -phenol, the problems such as that there are yields is lower for the route, and diazotising hydrolysis pollution is big.
Synthetic route 2:
The route hydrolyzes by methyl-etherified, nitrification, reduction, diazotising using benzyl carbinol as raw material, but equally exists pollution
Problem, and the price of benzyl carbinol is more expensive.
Synthetic route 3:
The route is using parahydroxyacet-ophenone as raw material, by α bromination, methoxy substitution, carbonyl reduction, but bromine
Bromine is used in change, pollutes larger, and reduction needs Zn-Hg or metal catalytic, the former pollutes larger, and the latter's price is costly.
Synthetic route 4:
The route is using as raw material, by bromo, methoxy substitution, but raw material is not easy to obtain to methoxybenzene ethyl alcohol
It arrives, bromo uses large excess of hydrobromic acid, and post-processing is difficult, and pollution is larger, and methoxy substitution is also required to use significantly excessive
Sodium methoxide, and yield is lower, higher cost.
The generally existing yield of technique for synthesizing p- (2- methoxyl group) ethyl -phenol at present in summary is low, at high cost, pollution
Greatly, the problems such as industrialization difficulty is big.Therefore there is an urgent need to improve these problems to realize p- (2- methoxyl group) ethyl for industrialization
The industrialization of phenol.
P- (2- methoxyl group) the ethyl -phenol preparation method of medicinal intermediate that invention provides is easy to operate, chemical reaction is received
Rate is high, the three wastes are few, cost of material is cheap, the finished product for the high-purity that can be arrived.
Summary of the invention
The object of the present invention is to provide one kind industrialized production, operation can be suitble to simple and relative inexpensiveness, purity
The novel preparation method of p- (2- methoxyl group) ethyl -phenol of relatively high medicinal intermediate.For this purpose, the synthetic route that the present invention uses
It is as follows:
In the present invention using parachlorophenol or p bromophenol as starting material, generated under acid catalysis with isobutene among
Body I generates intermediate II by formatting, with reacting ethylene oxide, then obtains p- 2- chloroethyl benzene under acting on thionyl chloride
Phenol finally carries out methoxy substitution and modifies to obtain p- (2- methoxyl group) ethyl -phenol
The present invention provides a kind of preparation method of p- (2- methoxyl group) ethyl -phenol of intermediate, the method includes with
Lower step:
1, parachlorophenol or p bromophenol and isobutene reaction protect phenolic hydroxyl group, obtain phenolic hydroxyl group protection parachlorphenol or
Person is to bromine phenol；
2, the parachlorphenol or carry out grignard reaction to bromine phenol and magnesium that phenolic hydroxyl group is protected obtain corresponding grignard reagent, and
Further with reacting ethylene oxide, the p-hydroxyphenylethanol of phenolic hydroxyl group protection is obtained；
3, the p-hydroxyphenylethanol of phenolic hydroxyl group protection carries out chloro and deprotection reaction with thionyl chloride at 10-100 DEG C, obtains
To p- 2- chloroethyl phenol；
4, p- 2- chloroethyl phenol and MOH or MOCH3、MHCO3Or M2CO3Effect, M is alkali or alkaline earth metal,
It carries out methoxy substitution and obtains p- (2- methoxyl group) ethylo benzene phenates, and be acidified and obtain p- (2- methoxyl group) ethyl -phenol.
A specific embodiment according to the present invention, parachlorophenol or p bromophenol and isobutene reaction in step 1
Phenolic hydroxyl group is protected, obtains the parachlorphenol of phenolic hydroxyl group protection or to bromine phenol, preferably parachlorophenol.
A specific embodiment according to the present invention, the parachlorphenol of phenolic hydroxyl group protection or to bromine phenol and magnesium in step 2
Carry out grignard reaction, obtain corresponding Grignard Reagent, and further with reacting ethylene oxide, obtain phenolic hydroxyl group protection to hydroxyl
The parachlorophenol of benzyl carbinol, preferably phenolic hydroxyl group protection.
A specific embodiment according to the present invention, in step 3 p-hydroxyphenylethanol of phenolic hydroxyl group protection -10~
100 DEG C carry out chloro and deprotection reaction with thionyl chloride, p- 2- chloroethyl phenol are obtained, preferably at 45-60 DEG C.
A specific embodiment according to the present invention, in step 4 p- 2- chloroethyl phenol alkali include MOH or
MOCH3、MHCO3Or M2CO3Under the action of, M is alkali metal, preferably Na, K, and alkali is most preferably NaOH or NaOCH3。
A specific embodiment according to the present invention, the present invention provides a kind of p- (2- methoxyl group) ethyl -phenols
Preparation method, it is characterised in that the following steps are included:
(1) p- 2- chloroethyl phenol in the presence of alkali, carries out methoxy substitution and reacts to obtain p- (2- methoxyl group) second
Base phenolate；
(2) p- (2- methoxyl group) ethyl -phenol is acidified to obtain p- (2- methoxyl group) ethyl -phenol,
The structure of p- 2- chloroethyl phenol, p- (2- methoxyl group) ethylo benzene phenates and p- (2- methoxyl group) ethyl -phenol
It is as follows respectively:
Wherein M is alkali metal or alkaline-earth metal, preferred as alkali, particularly preferred Na or K.
A specific embodiment according to the present invention, alkali used in step (1) are MOH or MOCH3、MHCO3Or
MCO3, M is alkali or alkaline earth metal, preferably M be alkali metal, particularly preferred M be Na or K, the alkali be preferably NaOH or
NaOCH3。
A specific embodiment according to the present invention, substitution reaction temperature is -10~100 DEG C in step (1), preferably 45
~60 DEG C.
A specific embodiment according to the present invention, in the presence of a solvent, the solvent is selected from first to step (1)
Alcohol, ethyl alcohol, toluene, dimethylbenzene, dichloroethanes, acetonitrile, acetone, tetrahydrofuran or DMF (Chinese, N, N- dimethyl formyl
Amine), the solvent is preferably methanol, DMF.
A specific embodiment according to the present invention, step (2) is middle to carry out the acid that acidification reaction uses as sulfuric acid, salt
Acid, phosphoric acid, nitric acid, acetic acid, preferably hydrochloric acid.
A specific embodiment according to the present invention, step carries out at -10~60 DEG C in (2), preferably 10~30
It is carried out at DEG C.
A specific embodiment according to the present invention, p- 2- chloroethyl phenol synthesize by the following method:
Using parachlorophenol or p bromophenol as raw material, intermediate compound I is generated under acid catalysis with isobutene；
Intermediate compound I generates intermediate II through grignard, with reacting ethylene oxide；
Intermediate II and thionyl chloride carry out chloro and deprotection reaction obtains p- 2- chloroethyl phenol, and wherein X is selected from Cl
Or Br.
A specific embodiment according to the present invention, intermediate II carry out chloro with thionyl chloride at 10-100 DEG C and take off
Protection reaction, obtains p- 2- chloroethyl phenol.
A specific embodiment according to the present invention, intermediate compound I and magnesium carry out grignard reaction, obtain Grignard Reagent, and
Further with reacting ethylene oxide, intermediate II is obtained.
A specific embodiment according to the present invention, X Cl.
Compared with the prior art, technical advance of the invention is:
1) compared to synthetic method before, this method by collapsing reaction, (for example depressurize by the purification for avoiding intermediate
The methods of distillation), substantially increase the convenience of operation.
2) more dangerous and pollution the technique such as nitrification, diazotising hydrolysis is avoided, environmentally friendly, the three wastes are less.
3) using parachlorophenol or p bromophenol as raw material, higher yields obtain the para hydroxybenzene second of tert-butyl protection
Alcohol is protected compared to methyl, and tert-butyl, which has, is preferably deprotected performance, and the condition of demethylation is more harsh (in thionyl chloride
Methyl cannot be successfully removed under 50-60 DEG C of effect), and yield is lower, tert-butyl deprotection reaction mild condition (50-60 DEG C),
And yield is higher (close to 100%).
4) in the third step compared to bromo for, the reaction of chloro is more easy, and yield (~95%) is than bromo
Yield is higher, does not need large excess of hydrobromic acid, advantage becomes apparent from environmental protection and cost.
5) in the technique for being introduced into methoxyl group, alkali, such as MOH or MOCH are utilized3Or MCO3Under the action of, obtain mesh
Compound is marked, is effectively avoided using the higher dimethyl suflfate of toxicity.
Method yield provided by the invention is relatively high, at low cost, pollution is few, thus is especially suitable for industrialized production.
Specific embodiment
Below with reference to embodiment, the present invention is further elaborated, but these embodiments do not constitute any limit to the present invention
System.
Embodiment 1:
115g parachlorophenol, 260g toluene are added in 1L four-hole boiling flask, the 3g concentrated sulfuric acid stirs evenly, and interior temperature is lower than -10 DEG C
It is slowly introducing 120g isobutene, 4h has led to, -10 DEG C of -0 DEG C of heat preservation 12h, and 120g 30%NaOH is added and is quenched, 60g 30%NaOH
It washes again once, 60g washing is primary, removes toluene, intermediate compound I-Cl (150g, purity 99.2%, yield 90%) is obtained after concentration.
Embodiment 2:
150g p bromophenol, 350g toluene are added in 1L four-hole boiling flask, the 5g concentrated sulfuric acid stirs evenly, and interior temperature is lower than -10 DEG C
It is slowly introducing 130g isobutene, 4h has led to, -10 DEG C of -0 DEG C of heat preservation 12h, and 120g 30%NaOH is added and is quenched, 60g 30%NaOH
It washes again once, 60g washing is primary, removes toluene, obtains intermediate compound I-Br (161g, purity 98.3%, yield after product concentration
81%).
Embodiment 3:
23g magnesium chips, 150g THF, N are added in 1L four-hole boiling flask2Protection, 65 DEG C of heating, the 150g that embodiment 1 is obtained
Intermediate compound I-Cl is dissolved in 150g THF and is slowly added to, and reaction solution is cooled to 0-10 DEG C, is slowly added dropwise by 72 DEG C of insulation reaction 16h
Ethylene oxide 43g, 10 DEG C of 2~3h of heat preservation after adding, are added dropwise 30% sulfuric acid solution of 300g, the extraction of 150g toluene, and organic phase is used again
100g washing is primary, dry, recycles toluene and THF, obtains intermediate II crude product 150g, purity 91%, yield 88%.Crude product can
120g sterling, purity 99% are obtained directly to carry out next step reaction or by being evaporated under reduced pressure purification.
Embodiment 4:
23g magnesium chips, 150g THF, N are added in 1L four-hole boiling flask2Protection, 65 DEG C of heating, 185g intermediate compound I-Br is dissolved in
200g THF is slowly added in reaction solution, and reaction solution is cooled to 0-10 DEG C, ethylene oxide is slowly added dropwise by 72 DEG C of insulation reaction 6h
43g, 10 DEG C of 2~3h of heat preservation after adding, are added dropwise 30% sulfuric acid solution of 300g, the extraction of 150g toluene, and organic phase is washed with 100g again
Once, dry, toluene and THF are recycled, intermediate II crude product 140g, purity 88%, yield 78% are obtained.Crude product can directly into
Row reacts in next step or obtains 105g sterling, purity 99% by being evaporated under reduced pressure purification.
Embodiment 5:
3 intermediate II crude product 150g, 200g toluene of embodiment is added in 1L four-hole boiling flask, 15g DMF is warming up to 55-60
DEG C, 104g SOCl is slowly added dropwise2, solution colour is deepened during dropwise addition, finishes, and 60 DEG C of heat preservation 2h are cooled to 10-30 DEG C, delays
Slow that 100g 10%NaOH solution quenching reaction is added dropwise, after stirring half an hour, liquid separation, organic phase is concentrated to get to 2- chloroethyl benzene
Phenol 119g, purity 90.5%, yield 96%, crude product can directly carry out next step reaction.
Embodiment 6:
Intermediate II (99% purity) 150g of embodiment 3,200g toluene, 15g DMF, heating are added in 1L four-hole boiling flask
To 55-60 DEG C, 104g SOCl is slowly added dropwise2, solution colour is deepened during dropwise addition, finishes, 60 DEG C of heat preservation 2h are cooled to 10-
30 DEG C, 100g 10%NaOH solution quenching reaction is slowly added dropwise, after stirring half an hour, liquid separation, by column layer after organic phase concentration
Analysis obtains 114g product (98.5% purity), yield 95%.
Embodiment 7:
In 1L four-hole boiling flask be added 98g NaOH, 300g methanol, 50 DEG C of heating dissolved clarifications, by embodiment 5 obtain to 2- chlorine
Ethyl -phenol crude product 119g is dissolved in 50g methanol, is slowly added dropwise in reaction solution, and 1h is added, and 50 DEG C of insulated and stirred 6h are cooled to
Hydrochloric acid is added dropwise in room temperature, and adjusting PH is 5-6, the extraction of 100g toluene is added, liquid separation, after organic phase concentration, crude product is by vacuum distillation
Purification obtains sterling 94g, purity 99.7%, yield 90%.
Embodiment 8:
130g NaOCH is added in 1L four-hole boiling flask3, 300g methanol, 50 DEG C of heating dissolved clarifications, by embodiment 5 obtain to 2-
Chloroethyl phenol crude product 119g is dissolved in 50g methanol, is slowly added dropwise in reaction solution, and 1h is added, 50 DEG C of insulated and stirred 6h, cooling
To room temperature, hydrochloric acid is added dropwise, adjusting PH is 5-6, the extraction of 100g toluene is added, liquid separation, after organic phase concentration, crude product is steamed by decompression
It evaporates purification and obtains sterling 98g, purity 99.4%, yield 92%.
Embodiment 9:
130g NaOCH is added in 1L four-hole boiling flask3, 300g DMF, 50 DEG C of heating dissolved clarifications, by embodiment 5 obtain to 2-
Chloroethyl phenol crude product 119g is dissolved in 50g DMF, is slowly added dropwise in reaction solution, and 1h is added, 50 DEG C of insulated and stirred 6h, cooling
To room temperature, hydrochloric acid is added dropwise, adjusting PH is 5-6, the extraction of 100g toluene is added, liquid separation, after organic phase concentration, crude product is steamed by decompression
It evaporates purification and obtains sterling 90g, purity 98.2%, yield 88%.
Above-mentioned detailed description is illustrating for one of them possible embodiments of the present invention, the embodiment not to
The scope of the patents of the invention is limited, all equivalence enforcements or change without departing from carried out by the present invention are intended to be limited solely by the technology of the present invention
In the range of scheme.
Claims (10)
1. a kind of preparation method of p- (2- methoxyl group) ethyl -phenol, it is characterised in that the following steps are included:
(1) p- 2- chloroethyl phenol in the presence of alkali, carries out methoxy substitution and reacts to obtain p- (2- methoxyl group) ethylo benzene
Phenates；
(2) p- (2- methoxyl group) ethylo benzene phenates carries out acidification reaction and obtains p- (2- methoxyl group) ethyl -phenol,
The structure of p- 2- chloroethyl phenol, p- (2- methoxyl group) ethylo benzene phenates and p- (2- methoxyl group) ethyl -phenol is distinguished
It is as follows:
Wherein M is alkali metal or alkaline-earth metal, preferred as alkali, particularly preferred Na or K.
2. according to the method described in claim 1, it is characterized in that alkali used is MOH, MOCH3、MHCO3Or M2CO3, M is alkali
Metal or alkaline-earth metal, preferably M are alkali metal, and particularly preferred M is Na or K, and the alkali is preferably NaOH or NaOCH3。
3. according to the method described in claim 1, it is characterized in that in step (1) substitution reaction temperature be -10~100 DEG C, it is excellent
Select 45~60 DEG C.
4. according to the method described in claim 1, it is characterized in that step (1) in the presence of a solvent, solvent choosing
From methanol, toluene, dimethylbenzene, dichloroethanes, acetonitrile, acetone, tetrahydrofuran or DMF, solvent is preferably methanol, DMF.
5. according to the method described in claim 1, it is characterized in that carried out in step (2) acid that uses of acidification reaction be sulfuric acid,
Hydrochloric acid, phosphoric acid, nitric acid, acetic acid, preferably hydrochloric acid, dilute sulfuric acid.
6. according to the method described in claim 1, it is characterized in that in step (2) -10~60 DEG C at a temperature of carry out, preferably
It is carried out at 10-30 DEG C.
7. according to the method described in claim 1, it is characterized in that p- 2- chloroethyl phenol synthesizes by the following method:
Using parachlorophenol or p bromophenol as raw material, intermediate compound I is generated under acid catalysis with isobutene；
Intermediate compound I generates intermediate II through grignard, with reacting ethylene oxide；
Intermediate II and thionyl chloride carry out chloro and deprotection reaction obtains p- 2- chloroethyl phenol,
Wherein X is Cl or Br.
8. according to the method described in claim 7, it is characterized in that intermediate II carries out chloro with thionyl chloride at 10-100 DEG C
And deprotection reaction, obtain p- 2- chloroethyl phenol.
9. according to the method described in claim 7, obtain Grignard Reagent it is characterized in that intermediate compound I and magnesium carry out grignard reaction,
And intermediate II further is obtained with reacting ethylene oxide.
10. according to the method described in claim 7, it is characterized in that X is Cl.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811635234.8A CN109651094B (en) | 2018-12-29 | 2018-12-29 | Preparation method of p- (2-methoxy) ethylphenol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811635234.8A CN109651094B (en) | 2018-12-29 | 2018-12-29 | Preparation method of p- (2-methoxy) ethylphenol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109651094A true CN109651094A (en) | 2019-04-19 |
| CN109651094B CN109651094B (en) | 2021-09-28 |
Family
ID=66117798
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811635234.8A Active CN109651094B (en) | 2018-12-29 | 2018-12-29 | Preparation method of p- (2-methoxy) ethylphenol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109651094B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111116328A (en) * | 2019-12-27 | 2020-05-08 | 江西美晶科技有限公司 | Preparation method of metoprolol intermediate |
| CN114702372A (en) * | 2022-03-25 | 2022-07-05 | 台州市前进化工有限公司 | Method for preparing high-purity 4- (2-methoxy) ethylphenol |
| CN115286783A (en) * | 2021-12-29 | 2022-11-04 | 常熟耐素生物材料科技有限公司 | Preparation method of m-pentadecenyl phenol polyether |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02256637A (en) * | 1988-12-23 | 1990-10-17 | Hokko Chem Ind Co Ltd | 2-(p-or m-tert-butoxyphenyl)ethylmethyl ether and synthesis thereof |
| JPH02256636A (en) * | 1988-12-13 | 1990-10-17 | Hokko Chem Ind Co Ltd | Synthesis of p-or m-(2-(methoxy)ethyl)phenol |
| CN1800128A (en) * | 2006-01-18 | 2006-07-12 | 上海应用技术学院 | Para-(2-methoxyl) ethylphenol synthesis method |
| CN107382683A (en) * | 2017-07-18 | 2017-11-24 | 荆门医药工业技术研究院 | A kind of synthetic method for preparing Metoprolol intermediate |
-
2018
- 2018-12-29 CN CN201811635234.8A patent/CN109651094B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02256636A (en) * | 1988-12-13 | 1990-10-17 | Hokko Chem Ind Co Ltd | Synthesis of p-or m-(2-(methoxy)ethyl)phenol |
| JPH02256637A (en) * | 1988-12-23 | 1990-10-17 | Hokko Chem Ind Co Ltd | 2-(p-or m-tert-butoxyphenyl)ethylmethyl ether and synthesis thereof |
| CN1800128A (en) * | 2006-01-18 | 2006-07-12 | 上海应用技术学院 | Para-(2-methoxyl) ethylphenol synthesis method |
| CN107382683A (en) * | 2017-07-18 | 2017-11-24 | 荆门医药工业技术研究院 | A kind of synthetic method for preparing Metoprolol intermediate |
Non-Patent Citations (1)
| Title |
|---|
| H. UMESHA SHETTY等: "Stereospecific Synthesis of Specifically Deuterated Metoprolol Enantiomers from Chiral Starting Materials", 《JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111116328A (en) * | 2019-12-27 | 2020-05-08 | 江西美晶科技有限公司 | Preparation method of metoprolol intermediate |
| CN115286783A (en) * | 2021-12-29 | 2022-11-04 | 常熟耐素生物材料科技有限公司 | Preparation method of m-pentadecenyl phenol polyether |
| CN115286783B (en) * | 2021-12-29 | 2023-10-17 | 常熟耐素生物材料科技有限公司 | Preparation method of m-pentadecenyl phenol polyether |
| CN114702372A (en) * | 2022-03-25 | 2022-07-05 | 台州市前进化工有限公司 | Method for preparing high-purity 4- (2-methoxy) ethylphenol |
| CN114702372B (en) * | 2022-03-25 | 2022-12-16 | 台州市前进化工有限公司 | Method for preparing 4- (2-methoxyl) ethylphenol |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109651094B (en) | 2021-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109651094A (en) | A kind of preparation method of p- (2- methoxyl group) ethyl -phenol | |
| US8779222B2 (en) | Method for producing 1,1,3-trichloro-1-propene | |
| CN108368126B (en) | Process for preparing 1, 3-benzodioxole heterocycles | |
| CN110372578A (en) | A kind of new chlorphenamine maleate synthetic method | |
| CN107285992B (en) | Preparation method of 1, 1, 2, 3-tetrachloropropene | |
| CN105967986A (en) | 3-hydroxyacetophenone synthesis method | |
| CN101735029B (en) | Synthesis method of hellebore aldehyde | |
| WO2014071545A1 (en) | Preparation method for 2-bromo-3-fluorobenzoic acid | |
| CN107056590B (en) | Industrial method for preparing and purifying 4, 4' -dimethoxy triphenylchloromethane | |
| CN105418388B (en) | Preparation method of flame retardant 2, 2-bis [3, 5-dibromo-4- (2, 3-dibromo-2-methylpropyloxy) phenyl ] propane | |
| CN105198829B (en) | A kind of Preparation Method And Their Intermediate and purposes than his intermediate of department | |
| CN115504870A (en) | Preparation method and application of 4-methoxy-2-naphthol | |
| CN107686440A (en) | A kind of preparation method of m-trifluoromethyl phenol | |
| CN107337576B (en) | Normal temperature catalytic synthesis of 2-bromo-5-fluorobenzotrifluoride | |
| CN108147972B (en) | Preparation method of vipatavir intermediate and analogue thereof | |
| CN109485541B (en) | Method for preparing 1H,1H, 2H-perfluoro-1-octene | |
| CN109134187B (en) | A kind of technique for the bromobenzene synthesizing high steric hindrance | |
| CN110041176B (en) | Preparation method of thermosensitive paper sensitizer ethylene glycol diphenyl ether | |
| CN109232544B (en) | Preparation method of prucalopride | |
| CN114163316A (en) | Method for preparing 4-bromo-2-methoxy-5-trifluoromethylbenzaldehyde | |
| CN106748671B (en) | Method for synthesizing 2-alkoxy-4-methylphenol from 2-bromo-4-methylphenol | |
| JP3268459B2 (en) | Method for producing acetophenones | |
| CN108689810A (en) | To the synthetic method of methoxy ethyl phenol | |
| CN108164408A (en) | A kind of novel synthesis of 7- halogen -1- indones | |
| CN107973753A (en) | A kind of method of phase-transfer Wittig reaction 4-Hydroxyphenyl hydantoin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |