CA1150316A - Process for the preparation of benzyl alcohol derivatives - Google Patents
Process for the preparation of benzyl alcohol derivativesInfo
- Publication number
- CA1150316A CA1150316A CA000371226A CA371226A CA1150316A CA 1150316 A CA1150316 A CA 1150316A CA 000371226 A CA000371226 A CA 000371226A CA 371226 A CA371226 A CA 371226A CA 1150316 A CA1150316 A CA 1150316A
- Authority
- CA
- Canada
- Prior art keywords
- derivative
- formula
- benzyl alcohol
- alpha
- benzyl
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical class OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 14
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical group COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000006482 condensation reaction Methods 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 150000008062 acetophenones Chemical class 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000008280 blood Substances 0.000 abstract description 2
- 210000004369 blood Anatomy 0.000 abstract description 2
- 230000003177 cardiotonic effect Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 101150041968 CDC13 gene Proteins 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- -1 p-methoxybenzyloxycarbonyl Chemical group 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 229940086542 triethylamine Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000007859 condensation product Substances 0.000 description 2
- YKCAEQUWYQHAPP-UHFFFAOYSA-N n-benzyl-2-(3,4-dimethoxyphenyl)ethanamine Chemical compound C1=C(OC)C(OC)=CC=C1CCNCC1=CC=CC=C1 YKCAEQUWYQHAPP-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/56—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups
- C07C215/58—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups with hydroxy groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
- C07C215/60—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by hydroxy groups with hydroxy groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain the chain having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/60—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/62—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
PROCESS FOR THE PREPARATION OF BENZYL ALCOHOL DERIVATIVES
Abstract of the Disclosure The invention relates to a process for the preparation of benzyl alcohol derivatives of the formula:
which compounds have an excellent blood sugar lowering activity and a cardiotonic acitivity. The process com-prises subjecting an .alpha.-halogenoacetophenone derivative of the formula:
wherein R1 is a hydroxy group-protecting group and x is a halogen atom, and a 3,4-dimethoxyphenethylamine derivative of the formula:
Abstract of the Disclosure The invention relates to a process for the preparation of benzyl alcohol derivatives of the formula:
which compounds have an excellent blood sugar lowering activity and a cardiotonic acitivity. The process com-prises subjecting an .alpha.-halogenoacetophenone derivative of the formula:
wherein R1 is a hydroxy group-protecting group and x is a halogen atom, and a 3,4-dimethoxyphenethylamine derivative of the formula:
Description
~1~3~6 This invention relates to a novel process for preparing benzyl alcohol derivatives of the formula:
OH
HO ~ NH CH2 2~oc 3 The above compounds [I] have advantageous properties.
For example, ~-(3,4-dimethoxyphenethylaminomethyl)-2-hydroxybenzyl alcohol has an excellent blood sugar lowering activity, and ~-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzyl alcohol has an excellent cardiotonic activity, and hence, these compounds are useful as medicines.
It is known that the benzyl alcohol derivatives [I]
can be prepared by various methods. For example, U.S.
Patent 4,032,575 discloses that the compound [I] can be prepared by the steps of condensing an ~-halo-monobenzyl-oxyacetophenone (A) with 3,4-dimethoxyphenethylamine (B) to give an ~-(3,4-dimethoxyphenethylamino)monobenzyloxy-acetophenone (C), optionally reducing the compound (C) to give an ~-(3,4-dimethoxyphenethylaminoethyl)-monobenzyloxy-benzyl alcohol (D), and then subjecting the compound (C) or (D) to catalytic hydrogenation. However, the method disclosed in this U.S. Patent has the drawbacks that the yield of the condensation product (C) decreases unless the valuable starting amine (B) is used in an excess amount, since the condensation product (C) is unstable and susceptible to self-condensation or further phenacylation;
:~151~316 and that the use of an excess amount of the amine does not necessarily result in high yield.
As a result of investigations made by the present inventors, it has now been found that, when one of the starting materials, i.e. the 3,4-dimethoxyphenethylamine derivative, is used after protecting the amino group, the reaction can proceed without undesirable side reactions and therefore the desired compounds [I~ can be prepared in high yield and purity.
According to the present invention, the desired compounds [I] can be prepared by subjecting an ~-halogen-acetophenone derivative [IIl and a 3,4-dimethoxyphenethyl-amine derivative [III] to a condensation reaction to give an ~-(3,4-dimethoxyphenethylamino)acetophenone derivative [IV] and subjecting the resulting compound to catalytic hydrogenation either directly or after converting the compound [IV] to an ~-3,4-dimethoxyphenethylaminomethyl)-benzyl alcohol derivative [V] by treating it with a reducing agent, as shown by the following reaction scheme:
o R O ~ XC330 ~ NH_R2 [II] \~ ~ [III]
. .
~5~316 Rl ~J N_CH2_CH2_~--OOCH3 [IV]
OH
Rl ~ N-cH2-cR2 ~ oC33 [v]
[I]
wherein Rl is a hydroxy group-protecting group which is removable by catalytic hydrogenation, R2 is an amino group-protecting group which is removable by catalytic hydrogenation, and X is a halogen atom.
In the above formula [I~] and [III], the group R
includes, for example, aralkyl groups (e.g. benzyl), ,., aralkyloxycarbonyl groups (e.g. benzyloxycarbonyl or p-methoxybenzyloxycarbonyl), and the like. A suitable example of the group Rl is benzyl. On the other hand, the group R2 includes, for example, aralkyloxycarbonyl groups (e.g. benzyloxycarbonyl or p-methoxybenzyloxy-carbonyl), aralkyl groups (e.g. benzyl or triphenylmethyl), and the like. Suitable examples of the group R2 are benzyl and benzyloxycarbonyl.
The process of the present invention is explained in more detail with reference to the above reaction steps as follows:
.
.
~15~316 [II] + [III] ~ [IV]
The condensation reaction of the ~-halogenoacetophenone derivative [II] and the 3,4-dimethoxyphenethylamine deriva-tive [III] is preferably carried out in an appropriate solvent in the presence or absence of an acid acceptor.
Suitable examples of the acid acceptor are organic bases, e.g. pyridine or triethylamine, and inorganic bases, e.g.
potassium carbonate or sodium hydroxide. When the organic bases are used in an excess amount as the acid acceptor, additional solvent is not required. However, examples of appropriate solvents are lower alkanols (e.g. methanol or ethanol), acetone, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, methylene chloride, chloroform, and the like. The reaction proceeds readily at a temperature of 0 to 100C, preferably l5 to 50C.
[IV] ~[V]
The reduction of the resultant ~-(3,4-dimethoxyphen-ethylamino)acetophenone derivative [IV] is carried out by treating it with a reducing agent in a suitable solvent.
Suitable examples of the reducing agent are alkali metal borohydrides (e.g. sodium borohydride, or lithium boro-hydride), lithium aluminum hydride and diborane, prefer-ably sodium borohydride. Examples of the solvent are lower alkanols (e.g. methanol or ethanol), ether, tetrahydrofuran and dioxane which are inert solvent. The reaction proceeds readily at a temperature of 0 to 80C, preferably 0 to 25C.
-~15~316 [IV]~ [I] and [V] ~[I]
The catalytic hydrogenation of the ~-(3,4-dimethoxyphen-ethylamino)acetophenone derivative [IV] and the ~-(3,4-dimethoxyphenethylaminomethyl)benzyl alcohol derivative [V] obtained above can be carried out by the conventional method, that is, by dissolving the compound [IV] (or [V]) or a salt thereof in an appropriate solvent, and shaking the mixture under a stream of hydrogen or stirring the mixture under hydrogen pressure in the presence of a catalyst, by which the protecting groups can readily be removed from the compounds. Suitable examples of the catalyst are platinum or palladium catalysts, e.g. platinum, platinum oxide, palladium black, palladium-carbon colloidal palladium, and the like. Suitable examples of the solvent are lower alkanols (e.g. methanol or ethanol), water, acetic acid, and the like. The reaction proceeds readily at a temperature of 0 to 50C and under hydrogen pressure of 1 to 5 kg/cm2.
The desired compounds [I] prepared according to the above procedure can readily be isolated from the reaction mixture in the usual manner, for instance, by filtering the reaction mixture to remove the catalyst, concentrating the filtrate under reduced pressure, and crystallizing the resulting residue from an appropriate solvent. Optionally, the crys-talline thus obtained is treated with an acid in the usual manner to obtain the desired compounds [I] in the form of a salt with an acid.
' ~L~5a:~3~6 The present invention is illustrated by the following Examples but is not limited thereto.
Example 1 (1) ~-Bromo-2-benzyloxyacetophenone (1.53 g), N-benzyl-3, 4-dimethoxyphenethylamine (1.50 g) and triethylamine (1.11 g) were dissolved in 15 ml of dimethylformamide, and the mixture was stirred at room temperature for 7 hours. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with 10 ~ hydrochloric acid, saline solution and aqueous sodium bicarbonate succes-sively and further washed with saline solution, and then dried and concentrated under reduced pressure to give oily-N-benzyl-~-(3,4-dimethoxyphenethylamino)-2-benzyloxyacetophenone (2.2 g~ 88.8 ~).
IR v lcmq-l 1670 Mass m/e : 495 (M ) NMR (CDC13,~ ): 3.82 (6H, s, OCH3), 5.05 (2H, s), 5.15 (2H, s) This product was converted into 1/2 oxalate in the usual manner, and recrystallized from methanol to give colorless needles, m.p. 213 - 215C (decomp.).
OH
HO ~ NH CH2 2~oc 3 The above compounds [I] have advantageous properties.
For example, ~-(3,4-dimethoxyphenethylaminomethyl)-2-hydroxybenzyl alcohol has an excellent blood sugar lowering activity, and ~-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzyl alcohol has an excellent cardiotonic activity, and hence, these compounds are useful as medicines.
It is known that the benzyl alcohol derivatives [I]
can be prepared by various methods. For example, U.S.
Patent 4,032,575 discloses that the compound [I] can be prepared by the steps of condensing an ~-halo-monobenzyl-oxyacetophenone (A) with 3,4-dimethoxyphenethylamine (B) to give an ~-(3,4-dimethoxyphenethylamino)monobenzyloxy-acetophenone (C), optionally reducing the compound (C) to give an ~-(3,4-dimethoxyphenethylaminoethyl)-monobenzyloxy-benzyl alcohol (D), and then subjecting the compound (C) or (D) to catalytic hydrogenation. However, the method disclosed in this U.S. Patent has the drawbacks that the yield of the condensation product (C) decreases unless the valuable starting amine (B) is used in an excess amount, since the condensation product (C) is unstable and susceptible to self-condensation or further phenacylation;
:~151~316 and that the use of an excess amount of the amine does not necessarily result in high yield.
As a result of investigations made by the present inventors, it has now been found that, when one of the starting materials, i.e. the 3,4-dimethoxyphenethylamine derivative, is used after protecting the amino group, the reaction can proceed without undesirable side reactions and therefore the desired compounds [I~ can be prepared in high yield and purity.
According to the present invention, the desired compounds [I] can be prepared by subjecting an ~-halogen-acetophenone derivative [IIl and a 3,4-dimethoxyphenethyl-amine derivative [III] to a condensation reaction to give an ~-(3,4-dimethoxyphenethylamino)acetophenone derivative [IV] and subjecting the resulting compound to catalytic hydrogenation either directly or after converting the compound [IV] to an ~-3,4-dimethoxyphenethylaminomethyl)-benzyl alcohol derivative [V] by treating it with a reducing agent, as shown by the following reaction scheme:
o R O ~ XC330 ~ NH_R2 [II] \~ ~ [III]
. .
~5~316 Rl ~J N_CH2_CH2_~--OOCH3 [IV]
OH
Rl ~ N-cH2-cR2 ~ oC33 [v]
[I]
wherein Rl is a hydroxy group-protecting group which is removable by catalytic hydrogenation, R2 is an amino group-protecting group which is removable by catalytic hydrogenation, and X is a halogen atom.
In the above formula [I~] and [III], the group R
includes, for example, aralkyl groups (e.g. benzyl), ,., aralkyloxycarbonyl groups (e.g. benzyloxycarbonyl or p-methoxybenzyloxycarbonyl), and the like. A suitable example of the group Rl is benzyl. On the other hand, the group R2 includes, for example, aralkyloxycarbonyl groups (e.g. benzyloxycarbonyl or p-methoxybenzyloxy-carbonyl), aralkyl groups (e.g. benzyl or triphenylmethyl), and the like. Suitable examples of the group R2 are benzyl and benzyloxycarbonyl.
The process of the present invention is explained in more detail with reference to the above reaction steps as follows:
.
.
~15~316 [II] + [III] ~ [IV]
The condensation reaction of the ~-halogenoacetophenone derivative [II] and the 3,4-dimethoxyphenethylamine deriva-tive [III] is preferably carried out in an appropriate solvent in the presence or absence of an acid acceptor.
Suitable examples of the acid acceptor are organic bases, e.g. pyridine or triethylamine, and inorganic bases, e.g.
potassium carbonate or sodium hydroxide. When the organic bases are used in an excess amount as the acid acceptor, additional solvent is not required. However, examples of appropriate solvents are lower alkanols (e.g. methanol or ethanol), acetone, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, methylene chloride, chloroform, and the like. The reaction proceeds readily at a temperature of 0 to 100C, preferably l5 to 50C.
[IV] ~[V]
The reduction of the resultant ~-(3,4-dimethoxyphen-ethylamino)acetophenone derivative [IV] is carried out by treating it with a reducing agent in a suitable solvent.
Suitable examples of the reducing agent are alkali metal borohydrides (e.g. sodium borohydride, or lithium boro-hydride), lithium aluminum hydride and diborane, prefer-ably sodium borohydride. Examples of the solvent are lower alkanols (e.g. methanol or ethanol), ether, tetrahydrofuran and dioxane which are inert solvent. The reaction proceeds readily at a temperature of 0 to 80C, preferably 0 to 25C.
-~15~316 [IV]~ [I] and [V] ~[I]
The catalytic hydrogenation of the ~-(3,4-dimethoxyphen-ethylamino)acetophenone derivative [IV] and the ~-(3,4-dimethoxyphenethylaminomethyl)benzyl alcohol derivative [V] obtained above can be carried out by the conventional method, that is, by dissolving the compound [IV] (or [V]) or a salt thereof in an appropriate solvent, and shaking the mixture under a stream of hydrogen or stirring the mixture under hydrogen pressure in the presence of a catalyst, by which the protecting groups can readily be removed from the compounds. Suitable examples of the catalyst are platinum or palladium catalysts, e.g. platinum, platinum oxide, palladium black, palladium-carbon colloidal palladium, and the like. Suitable examples of the solvent are lower alkanols (e.g. methanol or ethanol), water, acetic acid, and the like. The reaction proceeds readily at a temperature of 0 to 50C and under hydrogen pressure of 1 to 5 kg/cm2.
The desired compounds [I] prepared according to the above procedure can readily be isolated from the reaction mixture in the usual manner, for instance, by filtering the reaction mixture to remove the catalyst, concentrating the filtrate under reduced pressure, and crystallizing the resulting residue from an appropriate solvent. Optionally, the crys-talline thus obtained is treated with an acid in the usual manner to obtain the desired compounds [I] in the form of a salt with an acid.
' ~L~5a:~3~6 The present invention is illustrated by the following Examples but is not limited thereto.
Example 1 (1) ~-Bromo-2-benzyloxyacetophenone (1.53 g), N-benzyl-3, 4-dimethoxyphenethylamine (1.50 g) and triethylamine (1.11 g) were dissolved in 15 ml of dimethylformamide, and the mixture was stirred at room temperature for 7 hours. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with 10 ~ hydrochloric acid, saline solution and aqueous sodium bicarbonate succes-sively and further washed with saline solution, and then dried and concentrated under reduced pressure to give oily-N-benzyl-~-(3,4-dimethoxyphenethylamino)-2-benzyloxyacetophenone (2.2 g~ 88.8 ~).
IR v lcmq-l 1670 Mass m/e : 495 (M ) NMR (CDC13,~ ): 3.82 (6H, s, OCH3), 5.05 (2H, s), 5.15 (2H, s) This product was converted into 1/2 oxalate in the usual manner, and recrystallized from methanol to give colorless needles, m.p. 213 - 215C (decomp.).
(2) N-Benzyl-~-(3,4-dimethoxyphenethylamino)-2-benzyl-oxyacetophenone (2.0 g) obtained in (1) was dissolved in 40 ml of methanol and sodium borohydride (1.2 9) was added in portions to the solution, and the mixture was stirred under ice-cooling for 4 hours. The mixture was poured B
.
- .~
~54~316 into ice-water and extracted with ethyl acetate. The extract was washed with water, dried and then evaporated to give N-benzyl-~-(3,4-dimethoxyphenethylaminomethyl)-2-benzyloxybènzyl alcohol (2.0 g) as an oily substance in quantitative yield.
IR vliq-l: 3480 cm Mass m/e : 497 (M+), 284 (base) NMR (CDC13, ~): 3.3 (lH, bs., OH), 3.74 (3H, s, OCH3),
.
- .~
~54~316 into ice-water and extracted with ethyl acetate. The extract was washed with water, dried and then evaporated to give N-benzyl-~-(3,4-dimethoxyphenethylaminomethyl)-2-benzyloxybènzyl alcohol (2.0 g) as an oily substance in quantitative yield.
IR vliq-l: 3480 cm Mass m/e : 497 (M+), 284 (base) NMR (CDC13, ~): 3.3 (lH, bs., OH), 3.74 (3H, s, OCH3),
3.80 (3H, s, OCH3), 5.02 (2H, s, OCH2pH), 5.0 - 5.3 (lH,>~H ), 6.5 7.7 (17H, aromatic H) (3) Crude N-benzyl-~-(3,4-dimethoxyphenethylamino-methyl)-2-benzyloxybenzyl alcohol (1.9 g) obtained in (2) was dissolved in 40 ml of methanol and subjected to cata-lytic hydrogenation with 10 % palladium carbon (500 mg) in hydrogen gas stream under atmospheric pressure. After the reaction, the catalyst was removed by filtration. The filtrate was concentrated under reduced pressure to give ~-(3,4-dimethoxyphenethylaminomethyl)-2-hydroxy benzyl alcohol (1.1 g) as an oily substance. After converting the resultant oil into its succinate, the salt was recrystal-lized from methanol/ether to give crystalline ~-(3,4-di-methoxyphenethylaminomethyl)-2-hydroxybenzyl alcohol succinate (1.33 g), m.p. 142 - 143C.
The hydrochloride of this product had a m.p. of 141 -143C (recrystallized from ethanol/ether).
-- .
~15~)316 Example 2 N-Benzyl-~-(3,4-dimethoxyphenethylamino)-2-benzyloxy-acetophenone (600 mg), which was prepared in the same manner as described in Example 1 - (1), was dissolved in 30 ml of methanol and subjected to catalytic hydrogenation with 10 % palladium carbon (300 mg) until the stoichio-metric amount of hydrogen was absorbed. The reaction mixture was treated in the same manner as described in Example 1 - (3), whereby ~-(3,4-dimethoxyphenethylamino-methyl)-2-hydroxybenzyl alcohol succinate (280 mg) was obtained as colorless crystals, m.p. 142 - 143C.
The hydrochloride of this product had a m.p. of 141 -143C.
The product was identified with the standard specimen by thin layer chromatography and a mixed melting point test.
Example 3 (1) ~-Chloro-4-benzyloxyacetophenone (2.35 9), N-benzyl-3,4-dimethoxyphenethylamine (2.7 9) and triethyl-amine (2.0 g) was dissolved in 50 ml of ethanol and the mixture was refluxed for 18 hours. The reaction mixture was concentrated under the reduced pressure. The obtained residue was purified by silica gel chromatography (solvent;
ether : hexane = 1 : 1), whereby N-benzyl-~-(3,4-dimethoxyphenethylamino)-4-benzyloxyacetophenone (3.0 g, 60.6 %) was obtained as an oily substance.
:~5~3~6 g After converting the resultant oil to crystalline 1/2 oxalate, this salt was recrystallized from methanol to give colorless needles, m.p. 122 - 125C.
IR v NcUm-~ : 1695, 1600 Mass m/e : 495 (M ) NMR (CDC13,~; 3.77 (3H, s, OCH3), 3.82 (3H, s, OCH3),
The hydrochloride of this product had a m.p. of 141 -143C (recrystallized from ethanol/ether).
-- .
~15~)316 Example 2 N-Benzyl-~-(3,4-dimethoxyphenethylamino)-2-benzyloxy-acetophenone (600 mg), which was prepared in the same manner as described in Example 1 - (1), was dissolved in 30 ml of methanol and subjected to catalytic hydrogenation with 10 % palladium carbon (300 mg) until the stoichio-metric amount of hydrogen was absorbed. The reaction mixture was treated in the same manner as described in Example 1 - (3), whereby ~-(3,4-dimethoxyphenethylamino-methyl)-2-hydroxybenzyl alcohol succinate (280 mg) was obtained as colorless crystals, m.p. 142 - 143C.
The hydrochloride of this product had a m.p. of 141 -143C.
The product was identified with the standard specimen by thin layer chromatography and a mixed melting point test.
Example 3 (1) ~-Chloro-4-benzyloxyacetophenone (2.35 9), N-benzyl-3,4-dimethoxyphenethylamine (2.7 9) and triethyl-amine (2.0 g) was dissolved in 50 ml of ethanol and the mixture was refluxed for 18 hours. The reaction mixture was concentrated under the reduced pressure. The obtained residue was purified by silica gel chromatography (solvent;
ether : hexane = 1 : 1), whereby N-benzyl-~-(3,4-dimethoxyphenethylamino)-4-benzyloxyacetophenone (3.0 g, 60.6 %) was obtained as an oily substance.
:~5~3~6 g After converting the resultant oil to crystalline 1/2 oxalate, this salt was recrystallized from methanol to give colorless needles, m.p. 122 - 125C.
IR v NcUm-~ : 1695, 1600 Mass m/e : 495 (M ) NMR (CDC13,~; 3.77 (3H, s, OCH3), 3.82 (3H, s, OCH3),
4.46 (2H, s), 4.63 (2H, s), 5.12 (2H, s, OCH2ph ) (2) N-Benzyl-~-(3,4-dimethoxyphenethylamino)-4-benzyl-oxyacetophenone.l/2 oxalate (1.3 g) obtained in (1) was dissolved in 50 ml of methanol, and sodium borohydride (2.0 g) was added in portions to the solution under ice-cooling and the mixture was stirred overnight. After the reaction, the mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with water, dried and then evaporated to give N-benzyl-~-~3,4-dimethoxyphenethylaminomethyl)-4-benzyloxybenzyl alcohol (1.2 g) as a crude oil substance.
IR v lcm-l : 3440 Mass m/e : 497 (M+), 284 (base) NMR (CDC13,~): 3.75 (6H, s, OCH3), 3.93 (lH, bs, OH), 4.57 (lH, t, J = 6Hz, XoHH)t 4.97 (2H, s, OCH2ph), 6.5 - 7.5 (17H, aromatic H).
(3) N-benzyl-~-(3,4-dimethoxyphenethylaminomethyl)-4-benzyloxybenzyl alcohol (1.2 g) obtained in (2) was dissolved in 40 ml of methanol and subjected to catalytic hydrogenation with 10 % palladium carbon (400 mg) in a o .. :- ,.. . . ..
-3L15~316 - 10 ~
hydrogen gas stream under atmospheric pressure. After the reaction, the catalyst was removed by filtration.
The filtrate was concentrated under reduced pressure to give a-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzyl alcohol as an oily substance. The resultant oil was dissolved in ethyl acetate and hydrogen chloride in ether was added to the solution under ice-cooling. The precipit-ating amorphous substance was recrystallized from ethanol/
ether to give ~-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzyl alcohol hydrochloride (657 mg) as colorless needles, m.p. 164 - 167C.
The product was identified with the standard specimen by thin layer chromatography and a mixed melting point test.
Example 4 N-Benzyl-a- (3,4-dimethoxyphenethylamino)-4-benzyloxy-acetophenone (500 mg), which was prepared in the same manner as described in Example 3 - (3) was dissolved in 30 ml of methanol and subjected to catalytic hydrogenation with 10 % palladium carbon (250 mg) until the stoichio-metric amount of hydrogen was absorbed. The reaction mixture was treated in the same manner as described in Example 3 - (3), whereby a-(3,4-dimethoxyphenethylamino-methyl)-4-hydroxybenzyl alcohol hydrochloride (180 mg) was obtained as colorless needles, m.p. 164 - 167C.
The product was identified with the standard specimen by thin layer chromatography and a mixed melting point test.
, '
IR v lcm-l : 3440 Mass m/e : 497 (M+), 284 (base) NMR (CDC13,~): 3.75 (6H, s, OCH3), 3.93 (lH, bs, OH), 4.57 (lH, t, J = 6Hz, XoHH)t 4.97 (2H, s, OCH2ph), 6.5 - 7.5 (17H, aromatic H).
(3) N-benzyl-~-(3,4-dimethoxyphenethylaminomethyl)-4-benzyloxybenzyl alcohol (1.2 g) obtained in (2) was dissolved in 40 ml of methanol and subjected to catalytic hydrogenation with 10 % palladium carbon (400 mg) in a o .. :- ,.. . . ..
-3L15~316 - 10 ~
hydrogen gas stream under atmospheric pressure. After the reaction, the catalyst was removed by filtration.
The filtrate was concentrated under reduced pressure to give a-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzyl alcohol as an oily substance. The resultant oil was dissolved in ethyl acetate and hydrogen chloride in ether was added to the solution under ice-cooling. The precipit-ating amorphous substance was recrystallized from ethanol/
ether to give ~-(3,4-dimethoxyphenethylaminomethyl)-4-hydroxybenzyl alcohol hydrochloride (657 mg) as colorless needles, m.p. 164 - 167C.
The product was identified with the standard specimen by thin layer chromatography and a mixed melting point test.
Example 4 N-Benzyl-a- (3,4-dimethoxyphenethylamino)-4-benzyloxy-acetophenone (500 mg), which was prepared in the same manner as described in Example 3 - (3) was dissolved in 30 ml of methanol and subjected to catalytic hydrogenation with 10 % palladium carbon (250 mg) until the stoichio-metric amount of hydrogen was absorbed. The reaction mixture was treated in the same manner as described in Example 3 - (3), whereby a-(3,4-dimethoxyphenethylamino-methyl)-4-hydroxybenzyl alcohol hydrochloride (180 mg) was obtained as colorless needles, m.p. 164 - 167C.
The product was identified with the standard specimen by thin layer chromatography and a mixed melting point test.
, '
Claims (4)
1. A process for the preparation of benzyl alcohol derivatives of the formula:
[I]
which comprises subjecting an .alpha.-halogenoacetophenone derivative of the formula:
[II]
wherein R1 is a hydroxy group-protecting group which is removable by catalytic hydrogenation, and X is a halogen atom, and a 3,4-dimethoxyphenethylamine derivative of the formula:
[I I I]
wherein R2 is an amino group-protecting group which is removable by catalytic hydrogenation, to a condensation reaction to give an .alpha.-(3,4-dimethoxyphenethylamino)aceto-phenone derivative of the formula:
[IV]
wherein R1 and R2 are as defined above, and subjecting the resulting compound to catalytic hydro-genation directly or after converting the compound to an .alpha.-(3,4-dimethoxyphenethylaminomethyl)benzyl alcohol derivative of the formula:
[V]
wherein R1 and R2 are as defined above, by treating it with a reducing agent.
[I]
which comprises subjecting an .alpha.-halogenoacetophenone derivative of the formula:
[II]
wherein R1 is a hydroxy group-protecting group which is removable by catalytic hydrogenation, and X is a halogen atom, and a 3,4-dimethoxyphenethylamine derivative of the formula:
[I I I]
wherein R2 is an amino group-protecting group which is removable by catalytic hydrogenation, to a condensation reaction to give an .alpha.-(3,4-dimethoxyphenethylamino)aceto-phenone derivative of the formula:
[IV]
wherein R1 and R2 are as defined above, and subjecting the resulting compound to catalytic hydro-genation directly or after converting the compound to an .alpha.-(3,4-dimethoxyphenethylaminomethyl)benzyl alcohol derivative of the formula:
[V]
wherein R1 and R2 are as defined above, by treating it with a reducing agent.
2. A process according to claim 1, wherein the groups R1 and R2 are both benzyl group.
3. A process according to claim 1, wherein the catalytic hydrogenation is carried out with palladium-carbon in a lower alkanol.
4. A process according to any one of claims 1, 2 or 3, wherein sodium borohydride is used as the re-ducing agent.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP21927/1980 | 1980-02-22 | ||
JP55021927A JPS609740B2 (en) | 1980-02-22 | 1980-02-22 | Production method of benzyl alcohol derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1150316A true CA1150316A (en) | 1983-07-19 |
Family
ID=12068692
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000371226A Expired CA1150316A (en) | 1980-02-22 | 1981-02-18 | Process for the preparation of benzyl alcohol derivatives |
Country Status (6)
Country | Link |
---|---|
JP (1) | JPS609740B2 (en) |
CA (1) | CA1150316A (en) |
CH (1) | CH645339A5 (en) |
ES (1) | ES499673A0 (en) |
NL (1) | NL8100857A (en) |
SE (1) | SE454172B (en) |
-
1980
- 1980-02-22 JP JP55021927A patent/JPS609740B2/en not_active Expired
-
1981
- 1981-02-06 SE SE8100853A patent/SE454172B/en not_active IP Right Cessation
- 1981-02-18 CA CA000371226A patent/CA1150316A/en not_active Expired
- 1981-02-20 ES ES499673A patent/ES499673A0/en active Granted
- 1981-02-20 NL NL8100857A patent/NL8100857A/en not_active Application Discontinuation
- 1981-02-20 CH CH115181A patent/CH645339A5/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
NL8100857A (en) | 1981-09-16 |
SE8100853L (en) | 1981-08-23 |
CH645339A5 (en) | 1984-09-28 |
SE454172B (en) | 1988-04-11 |
ES8202534A1 (en) | 1982-02-01 |
JPS56118045A (en) | 1981-09-16 |
ES499673A0 (en) | 1982-02-01 |
JPS609740B2 (en) | 1985-03-12 |
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