JP2001233869A - Optically active epoxypropionic acid ester derivative, its intermediate and method for producing thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an optically active epoxypropionic acid ester derivative useful as a synthetic intermediate of medicinal agents and agrochemicals and its intermediate and provide a method for producing thereof. SOLUTION: This optically active epoxypropionic acid ester derivative is obtained by epoxidizing a 1-phenyl-4,4-dimethyl-1-pentene-3-one in the presence of an asymmetric catalyst and subsequently oxidizing the epoxidized product.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an optically active epoxy propionate derivative, an intermediate thereof, and a method for producing the same. The optically active propionate derivative of the present invention is useful as a synthetic intermediate for pharmaceuticals and agricultural chemicals.

[0002]

2. Description of the Related Art As an optically active propionate derivative, a derivative in which a methoxy group is introduced at the 4-position (p-position) of a phenyl ring is known as a known synthetic intermediate of diltiazem (Japanese Patent Application Laid-Open No. 60-1985). -13776, JP-A-6-287183, etc.). However, the following equation (1)

[0003]

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[0004] An optically active epoxy propionic acid ester derivative represented by the formula (* represents an optically active carbon) is not known.

As a method for producing an optically active propionate derivative, a method for separating an optically active form from a racemate by an optical resolution method is known, but a production method for asymmetric synthesis is known. Absent.

[0006]

DISCLOSURE OF THE INVENTION The present invention relates to an optically active epoxypropionate derivative represented by the above formula (1), which is expected as a synthetic intermediate for pharmaceuticals and agricultural chemicals, and the following formula (2)

[0007]

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[0008] An object of the present invention is to provide a synthetic intermediate thereof represented by the formula (wherein, * represents an optically active carbon).
It is another object of the present invention to provide a method for producing them by an asymmetric synthesis method.

[0009]

Means for Solving the Problems The present inventors have conducted intensive studies on the creation of a novel optically active epoxy propionate derivative, and as a result, have found that the optically active epoxy propionate derivative represented by the above formula (1) The synthetic intermediate represented by the formula (2) was found. And
The present inventors have found a method for producing them by an asymmetric synthesis method, and have completed the present invention.

That is, the present invention provides an optically active epoxy propionate derivative represented by the above formula (1), an optically active epoxy enone derivative represented by the above formula (2),
And their production methods.

The present invention will be described in detail below.

The optically active epoxy propionic acid ester derivative of the present invention represented by the above formula (1) is specifically,
t-butyl (2S, 3R) -trans-2,3-epoxy-3- (4′-fluorophenyl) propionate, t-butyl (2S, 3R) -trans-2,3-
Epoxy-3- (3′-fluorophenyl) propionate, t-butyl (2S, 3R) -trans-2,3
-Epoxy-3- (2'-fluorophenyl) propionate, t-butyl (2R, 3S) -trans-2,
3-epoxy-3- (4′-fluorophenyl) propionate, t-butyl (2R, 3S) -trans-
2,3-epoxy-3- (3′-fluorophenyl) propionate, t-butyl (2R, 3S) -trans
-2,3-epoxy-3- (2'-fluorophenyl)
Propionate.

The optically active epoxy enone derivative represented by the above general formula (2) of the present invention is specifically (1R, 2
S) -trans-1,2-epoxy-1- (4'-fluorophenyl) -4,4-dimethyl-pentane-3-
ON, (1R, 2S) -trans-1,2-epoxy-1- (3′-fluorophenyl) -4,4-dimethyl-pentan-3-one, (1R, 2S) -trans-
1,2-epoxy-1- (2'-fluorophenyl)-
4,4-dimethyl-pentan-3-one, (1S, 2
R) -trans-1,2-epoxy-1- (4′-fluorophenyl) -4,4-dimethyl-pentane-3-
ON, (1S, 2R) -trans-1,2-epoxy-1- (3′-fluorophenyl) -4,4-dimethyl-pentan-3-one, (1S, 2R) -trans-
1,2-epoxy-1- (2'-fluorophenyl)-
4,4-dimethyl-pentan-3-one.

The above-mentioned compounds of the present invention are prepared by using known enones as raw materials, and

[0015]

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(Wherein, * represents optically active carbon).

That is, an optically active epoxy enone derivative represented by the above formula (2) is synthesized by an asymmetric epoxidation reaction of enones, and the compound is represented by the above formula (1) by further oxidizing the compound with an oxidizing agent. An optically active epoxy propionate derivative is synthesized.

As the catalyst used in the asymmetric epoxidation reaction of the present invention, any asymmetric epoxidation catalyst for enones can be used. However, the catalyst has low substrate selectivity and provides high yield and high optical purity. (A) an optically active binaphthol,
(B) lanthanum triisopropoxide, (C) triphenylphosphine oxide, and (D) cumene hydroperoxide (hereinafter sometimes abbreviated as CMHP)
Alternatively, it is preferable to use a catalyst composition containing tertiary butyl hydroperoxide (hereinafter sometimes abbreviated as TBHP). As the composition ratio of the catalyst components, it is theoretically sufficient that each component is present in an equivalent amount, but in order to actually form a catalyst stably in the reaction system,
The optically active binaphthol (A) is usually used in an amount of from 1.0 to 3.0 per mole of (B) lanthanum triisopropoxide.
Mol, preferably 1.0 to 1.5 mol, (C) triphenylphosphine oxide is usually 0.1 to 10 mol,
Preferably 1 to 10 mol, (D) CMHP or TBHP
Is 1 to 20 mol, preferably 1 to 10 mol.

In the epoxidation reaction of the present invention, it is preferable that the catalyst component is prepared in advance in the reaction system as a catalyst solution and then used for the epoxidation reaction of enones.

In the epoxidation reaction of the present invention, (R)
When -binaphthol is used, the configuration at the 1-position and 2-position of the epoxy enones of the present invention gives (1R, 2S),
When (S) -binaphthol is used, (1S, 2R)
give.

In the epoxidation reaction of the present invention, the amount of the catalyst used is not particularly limited, but may be 0.01 to 50 based on the number of moles of lanthanum isopropoxide based on the substrate used in the reaction. The range of mol% is preferable, and the range of 0.1 to 25 mol% is more preferable.

As the solvent applicable to the epoxidation reaction of the present invention, any solvent can be used as long as it is a catalyst and a solvent inert to the epoxidation reaction. From the viewpoint, ether solvents such as dimethyl ether, diisopropyl ether, 1,2-dimethoxyethane, and tetrahydrofuran (hereinafter abbreviated as THF) are preferred, and among them, THF gives the highest result. These solvents can also be used as solvents when preparing the catalyst solution.

The amount of the solvent used is in the range of 2 to 200 times, more preferably 5 to 100 times, the weight of the enone used in the reaction.

The preparation time of the catalyst solution varies depending on the ratio of the components of the catalyst, the selection of the oxidizing agent, the type of the solvent, and the concentration of the catalyst, but is usually maintained at -50 ° C to 100 ° C for 0.5 to 4 hours. The color tone of the solution after the preparation of the catalyst exhibits yellowish green to dark green.

In the epoxidation reaction of the present invention, TBHP used as an oxidizing agent may be a commercially available solution of decane or the like, or may be extracted from 70% or 90% aqueous solution with toluene and dried with magnesium sulfate or the like. May be used in the present invention. CMHP may be used after purifying a commercially available 80% by weight product, or may be used as it is without purification.
By using P, a pure optically active substance can be obtained.

In the epoxidation reaction of the present invention, the above enones are added to a catalyst solution prepared in advance, and then CM is added.
It is preferable to carry out the reaction by supplying HP or TBHP.
The supply rate of the oxidizing agent is carried out under the condition that the oxidizing agent does not become excessively large in the system. Specifically, the reaction rate in the actual system is measured, and the supply rate is determined and carried out. When the feed rate is higher than the reaction rate, the yield may decrease, and when the feed rate is lower, the optical purity may decrease.

In the epoxidation reaction of the present invention, the amount of the oxidizing agent used is the same as the amount used for forming the catalyst and the amount added during the reaction, and is theoretically equivalent to the enones used in the reaction. Although sufficient, it is preferably used in an amount of 1.1 mol times or more to complete the reaction.

The reaction temperature in the epoxidation reaction of the present invention varies depending on the substrate of the enone.
The reaction is usually completed within 48 hours within a temperature range of -100 ° C.

In the epoxidation reaction of the present invention, zeolite is used, if necessary, for the purpose of dehydrating the inside of the system during preparation of the catalyst and during the reaction, and for accelerating the catalyst formation reaction and the epoxidation reaction. The zeolite can be used in any quantitative ratio with respect to the enone, but is usually used in an amount of about 10 mg to 2 g per 1 mmol of the enone. Examples of the type of zeolite include A-type zeolites represented by molecular sieves 3A, 4A, and 5A, molecular sieves 13X, Y-type, and L-type.
Although various zeolites such as types can be applied, molecular sieve 4A is preferable.

After completion of the epoxidation reaction, the optically active epoxy enones of the present invention can be obtained in high yield and high optical purity by purifying by post-treatment, column chromatography and the like.

The method for obtaining the optically active epoxy propionate of the present invention is not particularly limited. For example, the optically active epoxy enones obtained by the above method are oxidized by a Baeyer-Villiger reaction. The desired product is obtained.

As the oxidizing agent used in the Baeyer-Villiger reaction, all peracids and peroxides can be used, and without particular limitation, potassium persulfate, hydrogen peroxide and perbenzoic acid are among them. , M-chloroperbenzoic acid, CMHP, TBHP and the like.
Usually, the reaction is carried out at a temperature in the range of 0 ° C. to 150 ° C. for 1 to 48 hours to induce the desired product. In addition, depending on the type of the peracid and the peroxide, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, and lithium hydroxide may be used in combination in a water-alcohol solvent.

The amount of the oxidizing agent used in the Baeyer-Villiger reaction is usually 1 to 10 times the molar amount of the epoxy enone used in the reaction, and more preferably 2 to 10 times.
It is in the range of up to 5-fold molar amount.

After the Baeyer-Villiger reaction is completed, the peracid or peroxide is deactivated, followed by extraction with an organic solvent, drying, concentration, and purification by column chromatography to obtain the desired optically active epoxypropionate. A derivative is obtained.

[0035]

Industrial Applicability The optically active epoxy propionate derivative of the present invention has a high optical purity and can be used for various pharmaceuticals,
Expected as an important intermediate of pesticides.

[0036]

EXAMPLES The present invention will be described below in detail with reference to examples, but the present invention is not limited to the examples.
The analysis of the product was performed using the following equipment.

(Measurement of optical rotation) SORI manufactured by HORIBA
Use -300.

(Measurement of melting point) MP-500 manufactured by Yanaco Co., Ltd.
Use D.

(Measurement of ¹ H-NMR and ¹³ C-NMR) V
arian Gemini-200 (200MH
z).

(Measurement of MASS) Hitachi M-80B was used.

(IR measurement) A 2000FT-IR manufactured by Perkin Elmer was used.

(Test of Optical Purity) The test was performed by high performance liquid chromatography equipped with a chiral column AD of Daicel Co., Ltd., eluting solvent: Hexane / i-PrOH = 9.
The measurement was performed at 5/5 (vol / vol) at a flow rate of 1 ml / min.

Example 1 trans- (1R, 2S) -1,2-epoxy-1-
Synthesis of (2′-fluorophenyl) -4,4-dimethylpentan-3-one

[0044]

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A 50 mL eggplant-shaped flask containing a magnetic stirrer was charged with Molecular Sieves 4A (687 m).
g, 180 ° C. for 4 hours under reduced pressure) and heated with a heat gun for 3 minutes under reduced pressure by a vacuum pump to dry. After cooling to room temperature, triphenylphosphine oxide (574 mg, 2.06 mmol) and (R) -binaphthol (197 mg, 0.69 mmol) were added, and the reaction system was replaced with nitrogen gas. Then, THF (20m
L) was added and dissolved by stirring for 5 minutes.
Lanthanum isopropoxide (La (OiPr) 3,2
17 mg, 0.69 mmol) in THF (10 m
L), stirred for 1 hour, and further added CMHP (80
%, 127 μL, 0.69 mmol) and stirred for 1 hour to prepare a catalyst solution.

After confirming that the catalyst solution turned yellow-green, trans-1- (2'-fluorophenyl) -4,4-dimethyl-1-penten-3-one (2.84 g, 13.7 mmol) in THF (15 m
L) The solution was added and the reaction was started. After the reaction starts, CMH
P (80%, 3.17 mL, 17.2 mmol) in 20
Then, the mixture was stirred for 88 hours. The feed rate of CMHP was set at 20 hours based on the conversion rate of 5.0% / hrs as a result of the rate measurement by the equivalent reaction.

After completion of the reaction, 5.0 g of silica gel and 20 mL of methanol were added and stirred for 2 hours, followed by filtration, concentration, and silica gel column (hexane / ethyl acetate = 9/9).
By purifying in 1), trans- (1R, 2S)
-1,2-Epoxy-1- (2'-fluorophenyl)
-4,4-Dimethylpentan-3-one (1.62 g)
Was obtained as white crystals (yield 53%, optical purity 99ee).
%that's all).

Melting point: 61.0 to 62.5 ° C. ¹ H-NMR (CDCl ₃ ) δ 7.03 to 7.39 (m,
4H), 4.10 (d, 1H, J = 1.8 Hz), 3.
84 (d, 1H, J = 1.8 Hz), 1.25 (s, 9
H) ¹³ C-NMR (CDCl ₃ ) δ 207.8, 161.4
(J = 246.4 Hz), 130.1 (J = 8.1 H)
z), 126.2 (J = 3.5 Hz), 124.5 (J
= 3.5 Hz), 123.2 (J = 12.9 Hz), 1
15.4 (J = 20.2 Hz), 58.1, 54.3,
43.7, 25.7 IR (KBr; ν cm ^-1 ) 2978, 2935, 17
10, 1619, 1587, 1494, 1458, 14
16, 1248, 1217, 1099, 1077, 10
04,895,822,764,590,518 EI-MS (m / z) 222 (M ⁺ ) Specific rotation (c = 1.03, CHCl 3) [α] ²⁸ _D =
+191 Example 2 trans- (1R, 2S) -1,2-epoxy-1-
Synthesis of (3′-fluorophenyl) -4,4-dimethylpentan-3-one

[0049]

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Molecular sieves 4A (1.32 g) was placed in a 50 mL eggplant-shaped flask, and dried by heating with a heat gun for 3 minutes under reduced pressure by a vacuum pump. After cooling to room temperature, triphenylphosphine oxide (1.1
0 g, 3.97 mmol), (R) -binaphthol (3
79 mg, 1.32 mmol) and the reaction system was replaced with nitrogen gas. Next, THF (30 mL) was added and dissolved by stirring for 5 minutes, and then lanthanum isopropoxide (La (OiPr) 3, 418 mg, 1.3) was added.
2 mmol) in a THF solution (30 mL) and add 1
Stir for another hour and add CMHP (80%, 244 μL,
(1.32 mmol) and stirred for 1 hour to prepare a catalyst solution.

After confirming that the catalyst solution turned yellow-green, trans-1- (3'-fluorophenyl)-
4,4-dimethyl-1-penten-3-one (5.46
g, 26.4 mmol) in THF (27 mL) was added to initiate the reaction. After the start of the reaction, CMHP (80%,
6.11 mL, 33.1 mmol) in 12 hours,
Thereafter, the mixture was stirred for 127 hours. The supply rate of CMHP was set to 12 hours based on the conversion rate of 8.2% / hrs as a result of the rate measurement by the equivalent reaction.

After the completion of the reaction, 5.0 g of silica gel and 20 mL of methanol were added, followed by stirring for 2 hours, followed by filtration, concentration and
By purifying with a silica gel column (hexane / ethyl acetate = 9/1), trans- (1R, 2S) -1,
2-epoxy-1- (3′-fluorophenyl) -4,
4-Dimethylpentan-3-one (3.04 g) was obtained as white crystals (yield 52%, optical purity 99ee% or more).

Melting point: 68.0-69.5 ° C. ¹ H-NMR (CDCl ₃ ) δ 6.97-7.40 (m,
4H), 3.86 (d, 1H, J = 1.8 Hz);
81 (d, 1H, J = 1.8 Hz), 1.24 (s, 9
H) ¹³ C-NMR (CDCl ₃ ) δ 207.7, 163.1
(J = 245.7 Hz), 138.3 (J = 7.5 H)
z), 130.4 (J = 8.1 Hz), 121.5 (J
= 2.9 Hz), 116.0 (J = 25.3 Hz), 1
12.4 (J = 22.7 Hz), 59.0, 58.6
43.6, 25.7 IR (KBr; ν cm ^-1 ) 2975, 2937, 17
05, 1616, 1592, 1464, 1412, 13
97, 1275, 1230, 1140, 1075, 10
05,869,775,689,580,523 EI-MS (m / z) 222 (M ⁺ ) Specific rotation (c = 1.015, CHCl ₃ ) [α] ²⁷ _D =
+236 Example 3 trans- (1R, 2S) -1,2-epoxy-1-
Synthesis of (4'-fluorophenyl) -4,4-dimethylpentan-3-one

[0054]

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Molecular sieves 4A (869 mg) was placed in a 50 mL eggplant-shaped flask, and heated under a reduced pressure with a vacuum pump for 3 minutes with a heat gun and dried. After cooling to room temperature, triphenylphosphine oxide (725)
mg, 2.61 mmol), (R) -binaphthol (2
49 mg, 0.87 mmol) and the reaction system was replaced with nitrogen gas. Then, THF (25 mL) was added and dissolved by stirring for 5 minutes, and then lanthanum isopropoxide (La (OiPr) 3, 275 mg, 0.8 g) was added.
7 mmol) in a THF solution (35 mL).
Stir for another hour and add CMHP (80%, 321 μL,
(1.74 mmol) was added and stirred for 1 hour to prepare a catalyst solution.

After confirming that the catalyst solution turned yellow-green, trans-1- (4'-fluorophenyl)-
4,4-dimethyl-1-penten-3-one (3.60
g, 17.4 mmol) in THF (45 mL) was added to initiate the reaction. After the start of the reaction, CMHP (80%,
3.85 mL, 20.9 mmol) was added dropwise in 12 hours,
Thereafter, the mixture was stirred for 8 hours. The supply rate of CMHP was set to 12 hours based on the conversion rate of 8.5% / hr as a result of the rate measurement by the equivalent reaction.

After completion of the reaction, 5.0 g of silica gel and 20 mL of methanol were added and stirred for 2 hours, followed by filtration, concentration, and silica gel column (hexane / ethyl acetate = 9/9).
By purifying in 1), trans- (1R, 2S)
-1,2-Epoxy-1- (4'-fluorophenyl)
-4,4-Dimethylpentan-3-one (1.73 g)
Was obtained as white crystals (yield 45%, optical purity 99ee).
%that's all).

Melting point: 65.8-66.5 ° C. ¹ H-NMR (CDCl ₃ ) δ 7.02-7.32 (m,
4H), 3.85 (d, 1H, J = 1.8 Hz);
82 (d, 1H, J = 1.8 Hz), 1.24 (s, 9
H) ¹³ C-NMR (CDCl ₃ ) δ 207.9, 163.1
(J = 246.5 Hz), 130.0 (J = 144.6)
Hz), 127.4 (J = 8.2 Hz), 115.8
(J = 21.9 Hz), 59.1, 58.7, 43.
6,25.7 IR (KBr; ν cm ^-1 ) 2974, 2936, 17
14, 1606, 1514, 1478, 1436, 13
98,1223,1157,1075,1004,89
2,842,786,555,528 EI-MS (m / z) 222 (M ⁺ ) Specific rotation (c = 1.035, CHCl ₃ ) [α] ²⁸ _D =
Example 4 tert-butyl (2S, 3R) -trans-2,
Synthesis of 3-epoxy-3- (2'-fluorophenyl) propionate

[0059]

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The trans- (1) obtained in Example 1 was placed in a 100 ml eggplant-shaped flask equipped with a magnetic stirrer.
R, 2S) -1,2-epoxy-1- (2′-fluorophenyl) -4,4-dimethylpentan-3-one (5
00 mg, 2.25 mmol) and m-chloroperbenzoic acid (80% mCPBA, 1.94 g, 9.00 mmol)
After l) was dissolved in 15 mL of toluene, the mixture was heated on an oil bath and reacted at 90 ° C. for 19 hours. After the reaction solution was cooled to room temperature, the precipitate and the adsorbed material were removed by a silica gel short column, and then washed with 100 mL of dichloromethane. The obtained eluate was concentrated and dried under reduced pressure to obtain a residue, which was then purified by a silica gel column (hexane / ethyl acetate = 9/1) to give tert-butyl t.
rans- (2S, 3R) -2,3-epoxy-3-
(2'-fluorophenyl) propionate (307m
g) was obtained as a colorless transparent oil (yield 57%, optical purity 99ee% or more).

¹ H-NMR (CDCl ₃ ) δ 7.02-
7.37 (m, 4H), 4.30 (d, 1H, J = 1.
8 Hz), 3.41 (d, 1H, J = 1.8 Hz),
^{1.52 (s, 9H) 13 C} -NMR (CDCl 3) δ166.9,161.6
(J = 246.7 Hz), 130.1 (J = 8.1 H)
z), 126.3 (J = 3.3 Hz), 124.4 (J
= 3.6 Hz), 122.9 (J = 12.6 Hz), 1
15.4 (J = 20.7 Hz), 82.9, 56.7,
52.3, 28.0 IR (neat; ν cm ⁻¹ ) 2982, 2936, ¹
746, 1620, 1590, 1496, 1459, 1
424, 1370, 1343, 1307, 1253, 1
226, 1158, 970, 895, 759 EI-MS (m / z) 238 (M ⁺ ) Specific rotation (c = 1.100, CHCl ₃ ) [α] ²⁸ _D =
+119 Example 5 tert-butyl (2S, 3R) -trans-2,
Synthesis of 3-epoxy-3- (3'-fluorophenyl) propionate

[0062]

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The trans- (1) obtained in Example 2 was placed in a 100 ml eggplant-shaped flask equipped with a magnet stirrer.
(R, 2S) -epoxy-1- (3-fluorophenyl)
-4,4-dimethylpentan-3-one (514 mg,
2.31 mmol) and m-chloroperbenzoic acid (80%
mCPBA, 1.40 g, 6.47 mmol) was dissolved in 15 mL of toluene, and then heated on a hot water bath.
A time reaction was performed. After the reaction solution was cooled to room temperature, a precipitate and an adsorbed substance were removed by a silica gel short column, and then washed with 100 mL of dichloromethane. The residue obtained by concentrating the solvent of the eluate and drying under reduced pressure is then purified by a silica gel column (hexane / ethyl acetate = 9/1) to give tert-butyl trans- (2S, 3).
R) -2,3-Epoxy-3- (3'-fluorophenyl) propionate (178 mg) was obtained as a colorless and transparent oil (yield 32%, optical purity 99% or more).

¹ H-NMR (CDCl ₃ ) δ 6.94
7.38 (m, 4H), 4.02 (d, 1H, J = 1.
8 Hz), 3.37 (d, 1H, J = 1.8 Hz),
^{1.52 (s, 9H) 13 C} -NMR (CDCl 3) δ166.8,163.1
(J = 246.7 Hz), 138.1 (J = 7.4 H)
z), 130.3 (J = 8.2 Hz), 121.8 (J
= 2.9 Hz), 115.9 (J = 21.3 Hz), 1
12.7 (J = 22.7 Hz), 82.9, 57.5,
56.9, 28.0 IR (neat; ν cm ⁻¹ ) 2982, 2937, ¹
745, 1593, 1456, 1370, 1341, 1
237, 1157, 971, 962, 875, 779 EI-MS (m / z) 238 (M ⁺ ) Specific rotation (c = 1.205, CHCl ₃ ) [α] ²⁸ _D =
+150 Example 6 tert-butyl (2S, 3R) -trans-2,3
Of Epoxy-3- (4′-fluorophenyl) propionate

[0065]

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The trans- (1) obtained in Example 3 was placed in a 100 ml eggplant-shaped flask equipped with a magnet stirrer.
R, 2S) -Epoxy-1- (4′-fluorophenyl) -4,4-dimethylpentan-3-one (498 m
g, 2.24 mmol) and m-chloroperbenzoic acid (8
(0% mCPBA, 1.93 g, 8.96 mmol) was dissolved in 15 mL of toluene, heated, and reacted at 90 ° C. for 19 hours. After the reaction solution was cooled to room temperature, a precipitate and an adsorbed substance were removed by a silica gel short column, and then washed with 100 mL of dichloromethane. The eluate was concentrated and dried under reduced pressure, and the residue was purified by a silica gel column (hexane / ethyl acetate = 9/1) to give tert-butyl trans- (2S, 3R)-.
2,3-Epoxy-3- (4'-fluorophenyl) propionate (124 mg) was obtained as white crystals (yield 23%, optical purity 99ee% or more).

Melting point: 48.0-49.0 ° C. ¹ H-NMR (CDCl ₃ ) δ 7.01-7.31 (m,
4H), 4.01 (d, 1H, J = 1.8 Hz);
37 (d, 1H, J = 1.8 Hz), 1.52 (s, 9
H) ¹³ C-NMR (CDCl ₃ ) δ 167.0, 163.1
(J = 246.2 Hz), 131.1 (J = 2.9H)
z), 127.7 (J = 8.4 Hz), 115.7 (J
= 21.8 Hz), 82.8, 57.4, 57.1, 2
8.0 IR (KBr; ν cm ^-1 ) 2990, 2942, 17
24, 1609, 1515, 1468, 1440, 14
07, 1369, 1230, 1158, 970, 87
7,841,821,792,770,696,55
6,530 EI-MS (m / z) 238 (M ⁺ ) Specific rotation (c = 1.030, CHCl ₃ ) [α] ²⁸ _D =
+142

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Claims (5)

[Claims] 1. An optically active epoxy propionic acid ester derivative represented by the following formula (1). Embedded image (In the formula, * indicates optically active carbon.) 2. An optically active epoxy enone derivative represented by the following formula (2). Embedded image (In the formula, * indicates optically active carbon.) 3. The following formula (3): 3. The method for producing an optically active epoxy enone derivative according to claim 2, wherein the enone derivative represented by the formula (1) is epoxidized in the presence of an asymmetric catalyst. 4. An asymmetric catalyst comprising (A) an optically active binaphthol, (B) lanthanum triisopropoxide,
(C) triphenylphosphine oxide, and (D)
The method for producing an optically active epoxy enone derivative according to claim 3, comprising cumene hydroperoxide or tertiary butyl hydroperoxide. 5. The method for producing an optically active epoxy propionate derivative according to claim 1, wherein the optically active epoxy enone derivative according to claim 2 is oxidized with an oxidizing agent.