JP2003212811A - Method for producing cyclohexenone long-chain alcohol - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To easily produce a cyclohexenone long-chain alcohol with decreased reaction steps on an industrial scale at a low production cost. <P>SOLUTION: The cyclohexenone long-chain alcohol expressed by general formula (1) (A is a 10-18C alkylene or alkenylene; and R<SP>1</SP>, R<SP>2</SP>and R<SP>3</SP>are each independently H or methyl) is produced by reacting a 3-alkoxy-2-cyclohexen-1- one derivative expressed by formula (2) (R<SP>4</SP>is a 1-5C alkyl) with a Grignard reagent of a 10-18C ω-halogenoalcohol having hydroxy group protected by silylation and hydrolyzing the reaction product. <P>COPYRIGHT: (C)2003,JPO

Description

DETAILED DESCRIPTION OF THE INVENTION [0001] TECHNICAL FIELD The present invention relates to a method for reducing the number of reaction steps.
Simple and industrially advantageous cyclohexenone long-chain alcohol
A method for producing the same. [0002] BACKGROUND OF THE INVENTION Nerve growth factor (NGF)
Especially abundant in horses and cerebral cortex, differentiation and growth of nerve cells
Is a trophic factor essential for promoting function maintenance and survival,
It is a factor that acts on cholinergic neurons in the brain. A
Ruzheimer's dementia is a degeneration of cholinergic neurons
Shedding is the major lesion, and nerve growth factor is administered into the brain
Attempts have been made to treat Alzheimer's dementia. However
However, this nerve growth factor has a molecular weight of 12,000.
Because it is a protein, it cannot cross the blood-brain barrier,
It is not practical as a treatment for immersion dementia. Against this
Low-molecular-weight cyclohexene long-chain alcohols are orally administered.
Transfer into the brain, pass through the blood-brain barrier, and excel at low concentrations
Has a nervous growth promoting effect and acts directly on neurites.
Useful as a preventive and therapeutic drug for brain diseases such as dementia
(Table 2001-51505).
8). [0003] Cyclohexenone long-chain alcohols are
Cyclohexanone or methyl-substituted 2-cyclohexene
Benzene-1-sulfonate in the presence of an acid
And then react with ethylene glycol
And then react with ω-halogenoalkanol.
And then acid treatment to remove the protecting group
It is manufactured in a complicated reaction process. For example, 3-meth
Starting with 3-cyclohexenone as a starting material,
Roxytetradecyl) -4-methyl-2-cyclohexe
When producing 1-one, seven reaction steps are required.
there were. [0004] As described above, the conventional system
The method for producing clohexenone long-chain alcohols involves a reaction step.
Complex, many, cumbersome and expensive to manufacture
Was disadvantageous. Therefore, an object of the present invention is to provide a reaction step
Low cost and simple, low production cost and industrial advantage
To provide a process for the production of a novel cyclohexenone long-chain alcohol
It is in. [0005] Means for Solving the Problems The present inventors have prepared a known substance.
Simple cyclohexene with few reaction steps as starting materials
After a diligent search for a method for producing non-long-chain alcohols,
Easily produced from the well-known 1,3-cyclohexanedione
Of the enol form of cyclohexenone
Grignard using protected ω-halogeno long chain alcohol
The reaction is simple and requires few reaction steps.
Low production cost and industrially advantageous long chain of cyclohexenone
Found that alcohol could be obtained and completed the present invention
Was. That is, the present invention provides the following general formula (2) [0007] Embedded image (Where R¹, R^TwoAnd R^ThreeAre each independently
R represents a hydrogen atom or a methyl group;^FourRepresents a group having 1 to 5 carbon atoms.
A alkoxy group)
A hydroxyl group is added to the clohexen-1-one derivative by silylation.
Of a protected ω-halogeno alcohol having 10 to 18 carbon atoms
Reacting the lignard reagent and then hydrolyzing
General formula (1) [0009] Embedded image Wherein A is an alkylene having 10 to 18 carbon atoms
R 1 represents an alkyl group or an alkenylene group;¹, R^TwoAnd R^ThreeIs before
Cyclohexenone length)
The present invention provides a method for producing a chain alcohol. [0011] BEST MODE FOR CARRYING OUT THE INVENTION The raw material of the present invention is represented by the general formula (2)
(Hereinafter referred to as compound (2))
And R¹, R^TwoAnd R^ThreeEach independently represents a hydrogen atom
But at least one of these is a methyl group
preferable. Specifically, R¹= CH_Three, R^Two= R^Three= H
And R¹= R^Two= R^Three= CH_ThreeIs especially good
Good. Also, R^FourRepresents an alkyl group having 1 to 5 carbon atoms
However, an ethyl group is particularly preferred. As the starting compound (2), 3-ethoxy
Xy-6-methyl-2-cyclohexen-1-one, 3
-Ethoxy-2,6-dimethyl-2-cyclohexene-
1-one, 3-methoxy-2,6,6-trimethyl-2
-Cyclohexen-1-one and the like are preferred. The starting compound (2) can be supplied at a low cost, for example.
Enolization of available 1,3-cyclohexanedione
And methylation. This enolization and
And methylation may be in any order.¹, R^Two
And R^ThreeIf all are hydrogen atoms, methylation is required
Absent. The enolization is carried out, for example, by
1,3-cyclohexanedione (e.g., 2
-Methyl-1,3-cyclohexanedione), acid catalyst
In the presence of an alcohol (R^FourOH)
It is done by. As the acid catalyst, p-toluenesulfo
Acid, sulfuric acid and the like. The reaction is performed in toluene and xylene
60-15 in a solvent such as methanol, methanol, ethanol, etc.
It may be performed at a temperature of 0 ° C. for 2 to 10 hours. Methylation can be carried out, for example, by
1,3-cyclohexanedione, for example,
Lithium obtained from kill lithium and diisopropylamine
Reaction with a lithiating reagent such as
And then react with a methylating agent such as methyl iodide.
Is performed by Here, for example, the lithiation reaction
For example, tetrahydrofuran of lithium diisopropylamine
Solution such as hexane and hexane at -80 to 0 ° C (for example, -7
8 ° C) and dissolved in tetrahydrofuran, hexane, etc.
1,3-cyclohex enolized as required
Sandione (preferably, 3-ethoxy-2-cyclohexyl)
(Xen-1-one). Also
In the methylation reaction, methyl iodide is added to the reaction mixture.
And then raise the temperature to 5-30 ° C (eg, room temperature)
It is preferable to carry out stirring for 12 hours. The compound (2) thus obtained is
Ω-halo having 10 to 18 carbon atoms in which a hydroxyl group is protected by silylation
React the genoalkanol Grignard reagent, then
Cyclohexenone long-chain alcohol by hydrolysis with
(1) is manufactured. Where the silylated carbon
Examples of ω-halogenoalkanols of Formulas 10 to 18 include
For example, the following equation (3) [0017] Embedded image (Where X is a halogen atom, A is the number of carbon atoms
10 to 18 alkylene groups or alkenylene groups,
R^Five, R⁶And R⁷Are each independently an alkyl having 1 to 8 carbon atoms
A compound represented by the following formula: here
X includes a chlorine atom, a bromine atom, an iodine atom and the like.
However, a bromine atom is preferred. A has 10 to 10 carbon atoms
18 linear or branched alkylene groups or alkenylene
A straight-chain or branched chain having 12 to 16 carbon atoms
An alkylene group is preferable, and a straight chain having 12 to 16 carbon atoms.
Alkylene groups are preferred, especially tetradecylene groups, pens
Tadecylene groups are preferred. R^Five, R⁶And R⁷as,
Each of methyl, ethyl, isopropyl, t-butyl
And a tyl group. The Grignard reagent used in the present invention can be prepared by a conventional method.
Ω-halogenoalkanol and silylation-protected
It is obtained by reacting gnesium. Reaction of compound (2) with Grignard reagent
Is the same as the usual Grignard reaction,
In an anhydrous solvent such as toluene or tetrahydrofuran.
It is preferably carried out at a temperature of 0.5 to 3 hours. The subsequent hydrolysis reaction is, for example, p
-Run in the presence of acids such as toluenesulfonic acid, hydrochloric acid, sulfuric acid, etc.
It is preferred that By this hydrolysis reaction, R^FourGroup,
Grignard reagent and silylation protecting group are eliminated
You. In each reaction of the present invention, the intermediate is isolated
May be subjected to the next reaction, but without isolation
May be applied. In the present invention, the reaction mixture
Washing, extraction,
Recrystallization, various chromatography, etc., alone or in combination
It is preferable to perform it. [0023] The present invention will be described in more detail with reference to the following examples.
I do. Example 1 3- (15-hydroxypentadecyl)-
2,4,4-trimethyl-2-cyclohexene-1-o
Synthesis (1) 3-ethoxy-2-methyl-2-
Synthesis of cyclohexen-1-one 3 g of 2-methyl-1,3-cyclohexanedione (2 g
3.8 mmol) of 30 mL of ethanol and 56 mL of toluene
Dissolved in the mixture, and 92 mg of paratoluenesulfonic acid (0.
47 mmol) was added. Heat the mixture to reflux for
Water / ethanol / toluene azeotrope (boiling point:
78 ° C.), and the remaining toluene is distilled off under reduced pressure.
I left. Silica gel column flash chromatography
By chromatography (ethyl ether / hexane: 8/2)
Purified, 3-ethoxy-2-methyl-2-cyclohexe
2.7 g (17.4 mmol) of 1-one were obtained. Yield 73% R_f(Ethyl ether / hexane: 80/20) = 0.
37¹ H-NMR (200MHz, CDCl_Three) δ: 1.32 (t,^ThreeJ = 7.00Hz, 3H, H-9),
1.67 (t,^FourJ = 1.49Hz, 3H, H-7), 1.94 (qn,^ThreeJ = 6.33Hz, 2H, H-
5), 2.31 (t,^ThreeJ = 6.62Hz, 2H, H-6), 2.51 (td,^ThreeJ = 6.12Hz,^FourJ
= 1.44Hz, 2H, H-4), 4.03 (q,^ThreeJ = 7.00Hz, 2H, H-8).¹³ C-NMR (50 MHz, CDCl_Three) δ: 7.4 (C-7), 15.4 (C-9), 21.1
(C-5), 25.4 (C-4), 36.4 (C-6), 63.5 (C-8), 115.1 (C-
2), 171.4 (C-3), 198.9 (C-1). (2) 3-ethoxy-2,6-dimethyl
Synthesis of 2-cyclohexen-1-one Diisopropylamide dissolved in 8 mL of tetrahydrofuran
2.35 mL (19.45 mmol) was cooled to -78 ° C,
12.96 mL (19.45 mmol) of n-butyl lithium
After the addition, the temperature was raised to 0 ° C. After stirring at 0 ° C for 2 hours,
The reaction solution was cooled to -78 ° C and dissolved in 5 mL of tetrahydrofuran.
3-ethoxy-2-methyl-2-cyclohexene
2 g (12.96 mmol) of -1-one was added, and after 1 hour,
1.21 mL (19.45 mmol) of methyl iodide was added.
Thereafter, the temperature was raised to room temperature. The reaction was stirred overnight and then water
After diluting with 100 mL, extract three times with ethyl ether
Was. The organic layer is collected, washed with aqueous sodium chloride solution,
Dried over magnesium acid, filtered and concentrated under reduced pressure.
The crude product is absorbed on silica and
By chromatography (ethyl ether / hexane: 4/6)
Purified, 3-ethoxy-2,6-dimethyl-2-cyclo
1.72 g (10.24 mmol) of hexen-1-one were obtained.
Was. Yield 79% R_f(Ethyl ether / hexane: 40/60) = 0.
9¹ H-NMR (200MHz, CDCl_Three) δ: 1.12 (d, 3H, H-8), 1.33 (t,^ThreeJ =
7.00Hz, 3H, H-10), 1.54-1.74 (m, 4H, H-5, H-7), 1.98-2.1
1 (m, 1H, H-5 '), 2.19-2.31 (m, 1H, H-6), 2.51-2.60 (m, 2H,
H-4), 4.04 (qd, J = 4.68Hz, J = 2.33Hz, 2H, H-9).¹³ C-NMR (50 MHz, CDCl_Three) δ: 7.4 (C-7), 15.3 and 15.7 (C-
8, C-10), 24.5 (C-5), 28.9 (C-4), 39.5 (C-6), 63.3 (C-
9), 114.3 (C-2), 170.2 (C-3), 201.2 (C-1). (3) 3-ethoxy-2,6,6-tri
Synthesis of methyl-2-cyclohexen-1-one Diisopropylamide dissolved in 3 mL of tetrahydrofuran
1.45 mL (10.34 mmol) was cooled to -78 ° C,
Add 8.7 mL (10.46 mmol) of n-butyllithium
After that, the temperature was raised to 0 ° C. After stirring at 0 ° C. for 2 hours, the reaction mixture
Was cooled to -78 ° C and dissolved in 6 mL of tetrahydrofuran.
3-ethoxy-2,6-dimethyl-2-cyclohexe
Add 1.47 g (8.72 mmol) of 1-one and add 1 hour
After that, 1.59 mL (10.46 mmol) of methyl iodide was added.
Then, the temperature was raised to room temperature. The reaction was stirred overnight, then
Diluted with water (100 mL) and extracted three times with ethyl ether
did. Collect the organic layer, wash with aqueous sodium chloride,
Dry over magnesium sulfate, filter, and concentrate under reduced pressure.
Was. The crude product is purified by silica gel column chromatography.
(Ethyl-ether / hexane: 4/6)
-Ethoxy-2,6,6-trimethyl-2-cyclohex
1.46 g (8.04 mmol) of sen-1-one were obtained. [0029] Yield 92.2% R_f(Ethyl ether / hexane: 40/60) = 0.
31¹ H-NMR (200MHz, CDCl_Three) δ: 1.03 (s, 6H, H-8, H-9), 1.30
(t,^ThreeJ = 7.01Hz, 3H, H-11), 1.64 (t,^FourJ = 1.6Hz, 3H, H-7), 1.7
5 (t,^ThreeJ = 6.27Hz, 2H, H-5), 2.51 (tq,^ThreeJ = 6.29Hz,^FourJ = 1.56H
z, 2H, H-4), 4.01 (q,^ThreeJ = 6.97Hz, 2H, H-10).¹³ C-NMR (50 MHz, CDCl_Three) δ: 8.0 (C-7), 15.4 (C-11), 22.6
(C-4), 24.7 (C-8, C-9), 34.7 (C-5), 39.5 (C-6), 63.2 (C
-10), 113.1 (C-2), 169.0 (C-3), 203.6 (C-1). (4) 15-bromo-1- (t-butyl)
Synthesis of (dimethylsiloxy) pentadecane (A) Synthesis of 1,15-pentadecanediol Pentadecanol dissolved in 150 mL of tetrahydrofuran
5 g (20.8 mmol) was cooled to 0 ° C.
Gradually add 1.2 g (31.2 mmol) of lithium lithium
After the addition, the temperature was raised to room temperature. Stir the reaction at room temperature for 3 days.
After stirring, add 200 mL of a saturated aqueous solution of tartaric acid at 0 ° C., and then
Extracted three times with ethyl ether. Collect the organic layer and add NaCl
Wash with aqueous thorium, dry over magnesium sulfate,
Filter and concentrate under reduced pressure to give 1,15-pentadecandio.
5.01 g (20.5 mmol) were obtained. 98.6% yield R_f(Hexane / ethyl acetate: 10/90) = 0.44 Melting point 84-85 ° C¹ H-NMR (200MHz, CDCl_Three) δ: 1.28 (s large, 22H, H-3 to H-
13), 1.56 (qn,^ThreeJ = 6.6Hz, 4H, H-2,14), 3.64 (t,^ThreeJ = 6.6Hz,
4H, H-1,15).¹³ C-NMR (50 MHz, CDCl_Three) δ: 26.5 (C-3,13), 29.9 (C-4 to
C-12), 33.7 (C-2, C-14), 62.1 (C-1, 15). (B) 15-bromo-pentadecane-1
-Synthesis of all 50 mL of 48% hydrogen bromide is slowly added to 1,15-pentadecane
5.08 g (20.8 mmol) of diol and cyclohexane
Add to the mixture with 50 mL and heat to reflux for 6 hours, then 2 layers
And the aqueous layer was extracted three times with hexane. Collect organic layers
Aqueous saturated sodium bicarbonate solution and sodium chloride
Wash with aqueous solution, dry over magnesium sulfate, and
Concentrated. The crude product is absorbed on silica and
Ram chromatography (hexane / ethyl acetate: 7 /
Purified in 3), 15-bromo-pentadecane-1-O
4.33 g (14.08 mmol) were obtained. Yield 68% R_f(Hexane / ethyl acetate: 60/40) = 0.47 61-63 ° C¹ H-NMR (200MHz, CDCl_Three) δ: 1.28 (s large, 22H, H-3 to H-
13), 1.57 (qn,^ThreeJ = 6.7Hz, 2H, H-2), 1.86 (qn,^ThreeJ = 6.8Hz, 2
H, H-14), 3.41 (t,^ThreeJ = 6.8Hz, 2H, H-15), 3.65 (t,^ThreeJ = 6.6H
z, 2H, H-1).¹³ C-NMR (50 MHz, CDCl_Three) δ: 25.5 (C-3), 28.1 (C-13), 28.
5 (C-12), 29.4 (C-4 toC-11), 32.7 (C-2, C-15), 33.8 (C-
14), 62.9 (C-1). (C) 15-bromo-1- (t-butyl)
Synthesis of dimethylsiloxy) -pentadecane 15-Bromo-pentade dissolved in 23 mL of methylene chloride
2.3 g (7.49 mmol) of can-1-ol were trimmed.
Tilamine 2.1 mL (14.98 mmol), t-butyldi
2.03 g (13.48 mmol) of methylsilyl chloride
And 457.6 mg (3.74 mm) of dimethylaminopyridine
ol) and stirred at room temperature for 1 hour. Then, the reaction solution
To the methylene chloride layer
(200 mL) and an aqueous layer (200 mL). Organic layer
Dry over magnesium sulfate, filter, and concentrate under reduced pressure.
Was. The crude product was purified by silica gel column flash chromatography.
Purified by chromatography (hexane / ethyl acetate: 99/1)
And 15-bromo-1- (t-butyldimethylsiloxy)
2.98 g (7.07 mmol) of b) -pentadecane
Was. Yield 94.4% R_f(Hexane: 100) = 0.43¹ H-NMR (200MHz, CDCl_Three) δ: 0.00 (s, 6H, Me), 0.85 (s, 9H, t
Bu), 1.21 (s large, 22H, H-3 to H-13), 1.33-1.46 (m, 2
H, H-2), 1.74-1.88 (m, 2H, H-14), 3.36 (t,^ThreeJ = 6.89Hz, 2H,
H-15), 3.55 (t,^ThreeJ = 6.52Hz, 2H, H-1).¹³ C-NMR (50 MHz, CDCl_Three) δ: -5.2 (Me), 26 (tBu), 28.2-2
9.7 (C-3 to C-13), 33 (C-15), 35 (C-2, C-14), 63 (C-1). (5) 3- (15-hydroxypentade)
Sil) -2,4,4-trimethyl-2-cyclohexene
Synthesis of -1-one 15-bromo-1- dissolved in 3 mL of anhydrous ethyl ether
(T-butyldimethylsiloxy) -pentadecane 1 g
(2.36 mmol) and 0.115 g of magnesium
After refluxing for 40 minutes, tetrahydrofuran 2
3-ethoxy-2,6,6-trimethyl- dissolved in mL
287.5 mg of 2-cyclohexen-1-one (1.57
mmol). After stirring for 4 hours, add 3 mL of 10% hydrochloric acid.
The reaction was further stirred for 17 hours. Hydrogen carbonate solution
Neutralized with sodium and extracted three times with ethyl ether.
The organic layer is collected, washed with aqueous sodium chloride solution,
The extract was dried over magnesium, filtered, and concentrated under reduced pressure. Crude
The product was purified by silica gel column chromatography (hexa
/ Ethyl acetate: 9/1 to 6/4, concentration gradient 5%)
3- (15-hydroxypentadecyl) -2,
4,4-trimethyl-2-cyclohexen-1-one 2
22.7 mg (0.61 mmol) were obtained. Yield 39% R_f(Hexane / ethyl acetate: 70/30) = 0.26 Melting point 29-30 ° C¹ H-NMR (200MHz, CDCl_Three) δ: 1.06 (s, 6H, H-22,23), 1.17
(m, 24H, H-8 a H-19), 1.47 (m, 2H, H-20), 1.68 (s, 3H, H-2
4), 1.72 (t, J = 7.14Hz, 2H, H-5), 2.07 (m, 2H, H-7), 2.33
(t, J = 6.9Hz, 2H, H-6), 3.55 (t, J = 6.64Hz, 2H, H-21).¹³ C-NMR (50 MHz, CDCl_Three) δ: 11.4 (C-24), 25.8 (C-19), 2
6.8 (C-22,23), 28.8 (C-8), 29.2-29.6 (C-10 a C-18), 3
0.5 (C-7), 30.9 (C-9), 32.7 (C-20), 34.2 (C-5), 36.2 (C-
4), 37.4 (C-6), 62.8 (C-21), 130.5 (C-2), 165.6 (C-3),
 199.1 (C-1). Example 2 3- (14-hydroxytetra
(Decyl) -4-methyl-2-cyclohexen-1-one
Synthesis of (1) 3-ethoxy-6-methyl-2-
Synthesis of cyclohexen-1-one Diisopropyl alcohol dissolved in 50 mL of tetrahydrofuran
3.4 mL (24.4 mmol) of the min were cooled to -78 ° C and n
8.2 mL (12.3 mmol) of -butyllithium were added.
Thereafter, the temperature was raised to 0 ° C. After stirring at 0 ° C. for 2 hours, the reaction solution was
Cooled to -78 ° C and dissolved in 3 mL of tetrahydrofuran
3-ethoxy-2-cyclohexen-1-one 1.54
g (11 mmol), and the reaction was continued for 2 hours.
After addition of 0.77 mL (12.4 mmol) of methyl, the mixture was cooled to room temperature.
The temperature rose. After stirring at room temperature for 18 hours, 100 mL of water was added.
And then extracted three times with 100 mL of ethyl ether. Yes
The organic layer was collected, washed with aqueous sodium chloride solution,
Dry over nesium, filter, evaporate under reduced pressure and concentrate
did. The crude product was purified by flash chromatography (d
(Ethyl ether / hexane: 40/60).
Ethoxy-6-methyl-2-cyclohexen-1-one
1.19 g (7.7 mmol) were obtained. Yield 73% R_f(Ethyl ether / hexane: 70/30) = 0.
41¹ H-NMR (200MHz, CDCl_Three) δ: 1.13 (d,^ThreeJ = 6.87Hz, 3H, H-7),
1.33 (t,^ThreeJ = 7.01Hz, 3H, OCH_TwoCH _Three), 1.68 (m, 1H, H-5), 2.03
(m, 1H, H-5 '), 2.26 (m, 1H, H-6), 2.39 (m, 2H, H-4), 3.85
(q,^ThreeJ = 7.04Hz, 2H, OCH _TwoCH_Three), 5.28 (s, 1H, H-2).¹³ C-NMR (50 MHz, CDCl_Three) δ: 15.03 (C-7), 16.28 (OCH_Two C
H_Three), 29.33 (C-4), 30.18 (C-5), 41.03 (C-6), 65.06 (OCH
_TwoCH_Three), 102.92 (C-2), 177.75 (C-3), 202.86 (C-1). (2) 3- (14-hydroxytetrade)
Sil) -4-methyl-2-cyclohexen-1-one
Synthesis 14-bromo-1- dissolved in 4 mL of anhydrous ethyl ether
(T-butyldimethylsiloxy) -tetradecane 1.8
14 g (4.45 mmol) and 0.216 g of magnesium
(8.9 mmol), and ethane dibromide was added dropwise.
The Nyar reaction was started and allowed to react for 30 minutes. Tetrahi
3-ethoxy-6-methyl- dissolved in 4 mL of drofuran
0.825 g of 2-cyclohexen-1-one (5.32
mmol). After stirring at room temperature for 24 hours, 10% hydrochloric acid 1
0 mL was added, and the mixture was further stirred and reacted for 24 hours. Reaction solution
Neutralize with 10 mL of saturated aqueous sodium hydrogen carbonate
Extracted three times with 15 mL of ether. Collect the organic layer and add NaCl
Wash with aqueous thorium, dry over magnesium sulfate,
After filtration, the mixture was concentrated under reduced pressure. The crude product is
Chromatography (ethyl ether / hexane: 70 /
30) and purified by 3- (14-hydroxytetradeci).
L) -4-Methyl-2-cyclohexen-1-one
768 g (2.74 mmol) were obtained. Yield 55% R_f(Ethyl ether / hexane: 70/30) = 0.
30 37-38 ° C¹ H-NMR (200MHz, CDCl_Three) δ: 1.18 (d,^ThreeJ = 7.13Hz, 3H, H-21),
 1.25-1.59 (m, 24H, H-8to H-19), 1.69-1.84 (m, 1H, H-5),
 2.01-2.57 (m, 6H, H-5 '/ H-7 / H-6 / H-7' / H-4 / H-6 '), 3.63
(t,^ThreeJ = 6.50Hz, 2H, H-20), 5.80 (s, 1H, H-2).¹³ C-NMR (50 MHz, CDCl_Three) δ: 17.82 (C-21), 25.76 (C-5), 2
7.20-32.82 (C-8 to C-19), 33.07 (C-4), 34.23 (C-7), 3
5.67 (C-6), 63.07 (C-20), 124.92 (C-2), 170.72 (C-3),
199.82 (C-1). [0043] EFFECT OF THE INVENTION The cyclohexenone long-chain alcohol of the present invention
Is simple and requires few reaction steps.
Low and industrially advantageous.

────────────────────────────────────────────────── ───
[Procedure amendment] [Date of submission] February 27, 2002 (2002.2.2)
7) [Procedure amendment 1] [Document name to be amended] Description [Item name to be amended] 0024 [Amendment method] Change [Content of amendment] (1) 3-ethoxy-2-methyl-2-
Synthesis of cyclohexen-1-one 3 g of 2-methyl-1,3-cyclohexanedione (2 g
(3.8 mmol) was dissolved in a mixture of 30 mL of ethanol and 56 mL of toluene, and 92 mg (0.1 mL) of paratoluenesulfonic acid was dissolved.
47 mmol) was added. After the mixture is heated to reflux for reaction, a water / ethanol / toluene azeotrope (boiling point: 78 ° C.)
Was distilled off, and then the remaining toluene was distilled off under reduced pressure.
The crude product was purified by silica gel column flash chromatography (ethyl ether / hexane: 8/2),
3-ethoxy-2-methyl-2-cyclohexene-1-
2.7 g (17.4 mmol) of ON were obtained.

   ────────────────────────────────────────────────── ─── Continuation of front page    (72) Inventor Patrick Noubert             France 67C84 Strasbourg, France             Blaze Pascal 5 France             RIKEN (72) Inventor Delphine Trangar             France 67C84 Strasbourg, France             Blaze Pascal 5 France             RIKEN (72) Inventor Shoji Yamada             Meiji Milk 2-2-1 Shinsuna, Koto-ku, Tokyo             Pharmaceutical Business Division (72) Inventor Yukio Oshiba             540 Narita, Oitawara-shi, Kanagawa Meiji Dairies Corporation             Company Pharmaceutical Division (72) Inventor Hirohito Suzuki             Meiji Milk 2-2-1 Shinsuna, Koto-ku, Tokyo             Pharmaceutical Business Division F term (reference) 4H006 AA02 AC22 AC25 AC44 AC80                       BB15 BE01

Claims (1)

[Claim 1] The following general formula (2): (Wherein, R ¹ , R ² and R ³ each independently represent a hydrogen atom or a methyl group, and R ⁴ represents an alkyl group having 1 to 5 carbon atoms) 3-alkoxy-2-cyclohexene- A 1-one derivative is reacted with a Grignard reagent of an ω-halogeno alcohol having 10 to 18 carbon atoms in which a hydroxyl group is protected by silylation, and then hydrolyzed. (Wherein, A represents an alkylene group or alkenylene group having 10 to 18 carbon atoms, and R ¹ , R ² and R ³ are the same as those described above).