Process for producing quinolinecarbaldehyde

Details Process for producing quinolinecarbaldehyde Process for producing quinolinecarbaldehyde

2001-07-09

2002-08-20

Davis, Zinna Northington (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

06437135

ABSTRACT:

This application is a 371 application of PCT/JP 99/06655 filed Nov. 29, 1999.
BACKGROUND OF THE INVENTION
1. Technical Field
The present invention relates to a process for producing a quinolinecarbaldehyde. More particularly, it relates to a process for easily and efficiently producing 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde which is useful as an intermediate for the synthesis of a HMG-CoA reductase inhibitor as a cholesterol-lowering drug.
2. Background Art
2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde is an intermediate useful as an intermediate for the synthesis of a HMG-CoA reductase inhibitor. Heretofore, as a method of oxidizing 2-cyclopropyl-4-(4-fluorophenyl)-3-hydroxymethylquinoline to 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde, an oxidation method employing chromic acid or a method of employing a dimethyl sulfoxide-dehydration agent (such as a Swern oxidation method), or a method of employing a nitroxyl radical-hypochlorite represented by TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy free radicals), has been used.
However, the above methods have a problem of waste liquid treatment due to formation of environmentally hazardous chromium ions or a problem of e.g. formation of badly smelling dimethyl sulfide, and in the case of nitroxyl radicals, the reagent is expensive and has a difficulty also in the chemical stability, and such can not be regarded as an industrially advantageous reaction.
SUMMARY OF THE INVENTION
Accordingly, the object of the present invention is to provide a process for simply and industrially advantageously producing 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde by oxidizing 2-cyclopropyl-4-(4-fluorophenyl)-3-hydroxymethylquinoline.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present inventors have studied various oxidation methods to solve such problems, and as a result, have found a production process which is free from the above-mentioned problem of waste liquid treatment or bad odor and which provides a good yield and is industrially advantageous, and they have arrived at the present invention.
Namely, the present invention provides a process for producing 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde of the formula (III):
characterized by oxidizing 2-cyclopropyl-4-(4-fluorophenyl)-3-hydroxymethylquinoline of the formula
with a salt of a hypohalogenous acid in the presence of a quaternary ammonium salt of the formula (II):
wherein each of R
1
, R
2
, R
3
and R
4
which are the same or different from one another, is a C
1-16
alkyl group or a benzyl group (the benzyl group may be substituted by a C
1-4
alkyl group, a C
1-4
alkoxy group or a halogen atom), and X
−
is a halogen ion, a sulfate ion or a methanesufonate ion.
According to the present invention, 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde which is a useful intermediate for the synthesis of a HMG-CoA reductase inhibitor, can be produced in good yield and industrially advantageously.
BEST MODE FOR CARRYING OUT THE INVENTION
Now, the present invention will be described in further detail.
Firstly, the terms for the respective substituents of R
1
R
2
, R
3
, R
4
and X
−
will be explained.
In this specification, “n” means normal, “i” iso, “s” secondary, “t” tertiary, “c” cyclo, and “o” ortho.
The C
1-4
alkyl group includes linear, branched and cyclic alkyl groups and may, for example, be methyl, ethyl, n-propyl, i-propyl, c-propyl, n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl and 2-methyl-c-propyl, preferably methyl and ethyl.
The C
1-16
alkyl group includes linear, branched and cyclic alkyl groups and may, for example, be methyl, ethyl, n-propyl, i-propyl, c-propyl, n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl, 2-methyl-c-propyl, n-pentyl, 1-methyl-n-butyl, 2-methyl-n-butyl, 3-methyl-n-butyl, 1,1-dimethyl-n-propyl, 1,2-dimethyl-n-propyl, 2,2-dimethyl-n-propyl, 1-ethyl-n-propyl, c-pentyl, 1-methyl-c-butyl, 2-methyl-c-butyl, 3-methyl-c-butyl, 1,2-dimethyl-c-propyl, 2,3-dimethyl-c-propyl, 1-ethyl-c-propyl, 2-ethyl-c-propyl, n-hexyl, 1-methyl-n-pentyl, 2-methyl-n-pentyl, 3-methyl-n-pentyl, 4-methyl-n-pentyl, 1,1-dimethyl-n-butyl, 1,2-dimethyl-n-butyl, 1,3-dimethyl-n-butyl, 2,2-dimethyl-n-butyl, 2,3-dimethyl-n-butyl, 3,3-dimethyl-n-butyl, 1-ethyl-n-butyl, 2-ethyl-n-butyl, 1,1,2-trimethyl-n-propyl, 1,2,2-trimethyl-n-propyl, 1-ethyl-1-methyl-n-propyl, 1-ethyl-2-methyl-n-propyl, 2-ethyl-2-methyl-n-propyl, c-hexyl, 1-methyl-c-pentyl, 2-methyl-c-pentyl, 3-methyl-c-pentyl, 1-ethyl-c-butyl, 2-ethyl-c-butyl, 3-ethyl-c-butyl, 1,2-dimethyl-c-butyl, 1,3-dimethyl-c-butyl, 2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl, 2,4-dimethyl-c-butyl, 3,3-dimethyl-c-butyl, 1-n-propyl-c-propyl, 2-n-propyl-c-propyl, 1-i-propyl-c-propyl, 2-i-propyl-c-propyl, 1,2,2-trimethyl-c-propyl, 1,2,3-trimethyl-c-propyl, 2,2,3-trimethyl-c-propyl, 1-ethyl-2-methyl-c-propyl, 2-ethyl-1-methyl-c-propyl, 2-ethyl-2-methyl-c-propyl, 2-ethyl-3-methyl-c-propyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl and n-hexadecyl.
The C
1-4
alkoxy group includes linear, branched and cyclic alkoxy groups and may, for example, be methoxy, ethoxy, n-propoxy, i-propoxy, c-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, c-butoxy, 1-methyl-c-propoxy and 2-methyl-c-propoxy, preferably methoxy and ethoxy.
The halogen atom may, for example, be a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, preferably a chlorine atom and a bromine atom.
The halogen ion may, for example, be a fluorine ion, a chlorine ion, a bromine ion and an iodine ion, preferably a chlorine ion and a bromine ion.
The salt of a hypohalogenous acid may specifically be sodium hypochlorite, calcium hypochlorite, potassium hypochlorite and sodium hypobromite, preferably sodium hypochlorite, calcium hypochlorite and potassium hypochlorite.
Preferred R
1
, R
2
, R
3
and R
4
may be methyl, ethyl, n-propyl, i-propyl, n-butyl, n-octyl, n-dodecyl and benzyl.
Preferred X
−
may be a chlorine ion and a bromine ion.
The following process may be mentioned as a preferred process in the present invention.
(1) A process for producing 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde of the formula [III] characterized by oxidizing 2-cyclopropyl-4-(4-fluorophenyl)-3-hydroxymethylquinoline of the formula [I] with sodium hypochlorite, calcium hypochlorite or potassium hypochlorite in the presence of a quaternary ammonium salt of the formula [II].
Now, a specific process for producing 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde will be explained.
The quaternary ammonium salt is added to a solution comprising 2-cyclopropyl-4-(4-fluorophenyl)-3-hydroxymethylquinoline and a solvent for the reaction, followed by stirring, and the salt of a hypohalogenous acid is added thereto, followed by stirring, whereby the desired 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde can be produced.
The solvent for the reaction is not particularly limited so long as it does not affect the reaction. For example, nitrites such as acetonitrile, propionitrile and butylonitrile, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, aromatic hydrocarbons such as benzene, toluene, xylene, mesitylene, chlorobenzene and o-dichlorobenzene, aliphatic hydrocarbons such as n-hexane, cyclohexane, n-octane and n-decane, esters such as methyl acetate, ethyl acetate and propyl acetate, halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform, ethers such as tetrahydrofuran, diethyl ether, t-butyl methyl ether and dimethoxy ethane, an amide such as N,N-dimethylformamide, N,N-dimethylacetoamide and N-methyl pyrrolidone, ureas such as 1,3-dimethylimidazolidinone and tetramethyl urea, preferably esters such as methyl acetate, ethyl acetate and propyl acetate, halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform, aromatic hydrocarbons such as toluene and xylene, and ketones such as acetone, methyl et

Affiliated with

Also associated with

Rating

Process for producing quinolinecarbaldehyde does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for producing quinolinecarbaldehyde, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for producing quinolinecarbaldehyde will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2957763