JPH04108778A - Optically active ester derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I [R<1> is alkyl; A is CH2 or CH(R<2>) (R<2> is alkyl; group shown by formula II is 5-membered ring containing asymmetric carbon; * is asymmetric carbon]. EXAMPLE:A compound shown by formula III. USE:An intermediate for medicines and agricultural chemicals and an intermediate for electronic materials such as liquid crystal materials, etc. PREPARATION:A compound shown by formula IV is made to react with an amide enolate derivative shown by formula V (R<3> is H or R<2>) in a solvent such as THF at -78 deg.C for 0.5-2 hours while stirring to give a compound shown by formula I. The compound shown by formula V is formed from an amide derivative shown by formula VI.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to optically active ester derivatives useful as intermediates for medicines and agricultural chemicals, or as intermediates for electronic materials such as liquid crystal materials.

[Conventional technology]

In recent years, optically active organic compounds have suddenly attracted attention not only in the medical and agricultural fields, but also in the information and electronic fields, such as liquid crystal materials, and are being actively researched.

Since optically active intermediates are required in the manufacturing process of these compounds, it is desired to develop a large number of intermediates in response to various demands.

[The problem that the invention attempts to solve! l] As a result of repeated studies aimed at establishing a new asymmetric organic synthesis method, the present inventor found that an ester derivative having a specific optically active group can be used in various asymmetric organic synthesis methods without impairing its optical properties. It was discovered that it is useful as a synthetic intermediate, and the present invention was completed.

[Means to solve the problem]

That is, the present invention relates to the general formula (I) (R1 represents an alkyl group, A is -CH!- or -C
B-(R'' represents an alkyl group), and is essentially a derivative.

The ester derivative of the present invention is represented by the general formula (1), and R1 is, for example, a methyl group, an ethyl group, an n-
Examples of R1 include linear or branched alkyl groups having 1 to 15 carbon atoms such as propyl group, n-butyl group, sec-butyl group, n-octyl group, and n-dodecyl group. group, ethyl group, n-propyl group, 1SO
- C1-C8 straight or branched alkyl groups such as propyl group, n-butyl group, n-octyl group, and the like.

The ester derivative of the present invention can be produced by the following reaction formula (a).

(u) (1)F2 [R1 in the general formula (ff) is the general formula CI''J
R3 in general formula [III] represents a hydrogen atom or R2 (R2 has the same meaning as in general formula (I)). ] This reaction is carried out at −78° C. in a solvent such as tetrahydrofuran at a temperature of 0.5
This can be carried out by stirring for ~2 hours.

In addition, the amide enolate derivative represented by the general formula (III) is usually prepared according to the following reaction formula (b)...Cb) (R3 in the general formula (IV) is represented by the general formula (III)
has the same meaning as in . ) is produced from the amide derivative represented by the general formula 1'lV), and the ester derivative of the general formula (II) is further added to this reaction system without isolation.
) Carry out the reaction of formula.

The reaction of reaction formula rb) can be carried out, for example, by reacting a base such as lithium diisopropylamide in a solvent such as tetrahydrofuran at -78° C. for 0.2 to 10 hours.

The optically active ester derivative represented by the general formula (I) of the present invention can be further hydrolyzed to obtain a dicarboxylic acid derivative [V] or a monocarboxylic acid derivative (VI), which can be obtained by the general formula ( It can be used for the same purpose as the optical ester derivative shown in 1).

C.F.

(R1 in general formula (VI), general formula [V], (Vl
A in l has the same meaning as in the general formula CL). ) [Effects of the Invention] The optically active ester derivative of the present invention is useful as an intermediate for pharmaceuticals and agricultural chemicals, or as an intermediate for electronic materials such as liquid crystal materials.

〔Example〕

The present invention will be explained in more detail with reference to examples, but the present invention is not limited to the following examples unless it exceeds the gist thereof.

Example 1 -CJt -C3H7 5d of anhydrous tetrahydrofuran (THF) and 0.3 (d (2.4 mmol) of diisopropylamine) were added to a nitrogen-substituted 30I11 double-bottomed flask, and the mixture was heated to -78°
n-butyllithium 0.96d (2.5M.

2.4 wa+of) was added dropwise and stirred at that temperature for 15 minutes to prepare lithium diisopropylamide.

i-C,)17-c3L a+mof) THF solution (2d) was slowly added dropwise at -78°C, and after further stirring for 30 minutes, ■CJs) 0.336 g (2,0mm+of) was slowly added dropwise. . Stir at this temperature for 1.5 hours, add 8 ml of IN hydrochloric acid, and then return to room temperature to stop the reaction.

After THF was distilled off from the second reaction solution under reduced pressure, the reaction mixture was extracted with diethyl ether (10dX3), and the organic layer was further washed with saturated brine (20d). This was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the desired ester derivative of the above structural formula was obtained by column chromatography (0,628 g (1,85 kg) (yield 93%).
)] was obtained.

' ``The diastereomer ratio is 89 from the FNMR integral ratio.
:ll was decided.

[Physical property values]

[α) i'-+2.59 (C=0.8266.C
HsOH)'HNMR(CDCj'1)id O,79
(d, J=6.'1lIz, 3)1).

1.03 (d, J = 6.6 Hz, 3 H),
1.32 (t, J = 7.1 Hz, 3 H)
, 2.39 (d ofsep, J = 6.6
Hz, 10.9 Hz, 18), 2.86(dd
, J = 8.4 Hz, 17.5 Hz, IH
).

3.08 (dd, J = 5.8 Hz, 17.5
Hz, LH).

3.30 (ta, IH), 3.78 (dd,
J = 11.9Hz, 3.5Hz, IH)+
3.87 (d, J = 7.7Hz, II()
, 3.95-4.30 (-, IH).

4.30 (q, J = 7.1 Hz, 2 H)
, 4.53(ddd, J = 10.9 Hz,
8.4 Hz, 3.5 Hz.

1B) "CNMR (CDCfz) ;d 13.95 (s
), 19.64 (s).

20.33 (s), 25.96 (s), 2
9.94' (q.

J = 2.3 H2), 37.13(q, J =
29.4 Hz).

49.35 (s), 61.99 (s) + 6
2.40 (s) 63.28 (s), 125.
72 (q, J engineering 280.2Hz), 167.3
0 (s), 168.08 (s).

169.88 (s) 19F NMR (CHzCj!z) i d 5.7
(d, J = 7.5 H2).

6.9 (d, J = 7.5 Hz) IR(ne
at); 2974.2880.1734.168
0 C11-'Example 2 1-CJ7 i-C3H.

Mi i-C,B.

to obtain the desired ester derivative of the above structural formula (
0,617g (1,75mmof), (yield 87%)
) was obtained.

The diastereomer ratio was measured by capillary gas chromatography, and it was found to be more than 99% diastereomerically pure.

[Physical property values]

(α)"+F・' = + 44.04 (C=1.
1044. CH30H)'HNMR (CDC1,)
id O,89(d, J = 6.8 Hz, 3
H).

0.92 (d, J = 7.2 Hz, 3 H),
1.18 (d, J = 7.0 Hz, 3
H), 1.27 (dd.

J = 7.4 Hz, 7.082.3)! ),
2.34 (dof sep, J = 7.0 Hz
, 3.4 Hz + L H).

2.58 (d, J = 6.2 Hz, 2)1
), 3.49 (qq, J = 9.0 Hz,
6.2 Hz, L H), 4.17 (dq, J
= 7.2 Hz, 2 H), 4.24 (ta
, 1B).

4.28 (m, L H), 4.31 (
ya, LH).

4.45 (quint, J = 3.6 Hz
, 1 [()13CNMR(CDCi!,s);
d 13.13 (s), 14.13 (s)
.

14.28 (s) + 18.06 (s)
+28.19 (s).

29.98 (q, J = 2.4 Hz), 35.
79(s).

41.04 (q, J = 26.2 Hz), 58
．． 90(s).

61.39 (s), 127.64 (Q+
J = 279.9Hz), 154.07 (s
), 171.28 (s ) + 174.65
(s)”F NMR (CHzCj!z); d 8.6
(d, J = 8.71(z)IR(neat)
; 2974. 2882. 1783. 1742
．． 1702am-'Example 3 Me-Cut Me-C5By -C3Hy was used, and the other operations were performed in the same manner to achieve the desired purpose.

Ester derivative of the above structural formula (0,735(1,93m
mof), (yield 97%)] was obtained.

The diastereomer ratio was measured in the same manner as in Example 2 and was found to be 98% or more diastereomerically pure.

[Physical property values]

(α)”o” =+62.70 (C=1.1314.
CH30H)'HNMR (CDCj!+) id O
, 88 (d, J = 6.9 Hz, 3 H).

0.94 (d, J = 7.0 Hz, 3 H) +
0.94 (d, length = 6.8 Hz, 3If)
, 1.01 (d, left = 6.8 Hz, 3 H)
, 1.28 (t, J = 7.1 Hz.

3 H), 2.17 (d of sep, J =
7.0Hz.

5.7 Hz, IH), 2.39 (dsep,
J = 7.111z, 3.3 Hz, IH)
, 2.58 (d, J = 7.0Hz, IH
), 2.58 (d, J = 5.8 Hz, L
H), 3.44 (dddq, J = 9.9 H
z, 8.4 Hz.

6.9 Hz, 5.5 Hz, 11'l), 4
．． 20 (q, J= 7.I Elz, 2
H), 4.24 (L I B )+4.
26 (■, 1 [1), 4.47 (dd, J
・9.9Hz, 5.511z, IH), 4.5
1 (ddd, J = 7.2 Hz, 4.8 Hz
, 3.3H2,IH)”CNMR(CD(/!z)
;d 14.13 (s ), 14.14 (s
).

14.27 (s), 17.50 (s)
, 18.15(s).

28.25 (s), 28.39 (s)
+31.35 (Q.

J = 2.8 Hz), 41.09 (q, J
= 25.7 Hz).

43.8Hz, J = 1.5Hz), 59.
09(s).

60.60 (s), 61.45 (s)
, 63.05 (s).

127.90 (q, J = 282.6) 1z
), 154.35 (s ), 171.09 (s
), 172.60 (s) 19F NMR (C
HzCfx) i d 10.1 (d, J =
8.1 Hz) Reference Example 1 0.353 g (1,0+u+
20d of THF/water mixed solution (THF:water=
3:1) and 35% hydrogen peroxide solution 0.3 at 0°C.
51d (4 mmof) and lithium hydroxide monohydrate 0
．． Slowly add 084g (2IIIlol),
Stir at that temperature for 20 minutes. NazSOs H to this
Aqueous solution (3d) of 7H201,1g (4,4mmof)
and 101 d of 0.5 sodium bicarbonate to stop the reaction.

After THF was distilled off under reduced pressure, 30I11 of water was added to the reaction mixture, and the mixture was extracted with methylene chloride (10dX3). 3N hydrochloric acid is added to the obtained aqueous layer to adjust the pH to 1 to 2, extracted with ethyl acetate, and the organic layer is dried over anhydrous magnesium sulfate.

By distilling off the solvent, CF3 CH3 84%).

[Physical property values]

'HNMR (CDCN3); d 1.26 (d,
J □ 7. OHz, 3H).

1.27 (t, J = 7.2 Hz, 3 H)
, 2.5 (d.

J = 6.4 Hz), 2.96 (m, I
H) + 3.41 (va, I HL 4.17 (q
, J = 7.2 Hz, IH), 11.9~1
2.7 (s, L H)”F NMR (CHxCjh
) ; d 7.7 (d, J = 9.4 Hz
) Reference Example 2 The reaction time was extended to 4 hours under the same conditions as Reference Example 1. Post-treatment was carried out as described above, and a white solid was obtained by distilling off the solvent. This was recrystallized from methylene chloride to obtain CF.

CH.

80%).

[Physical property values]

[α)zB・' = -16,94 (C = 0.8564.
CH13)'F4 NMR (CDCI!, s); d
1.23 (dq, J = 7.2 Hz, 0.
8Hz, 3H), 2.59 (d, J = 6
．． 4 Hz, 3H), 2.95 (dq, J =
3.7 Hz, 7.2 Hz.

IH), 3.40 (dtq, J = 6.4H
z, 3.7Hz, 9.7Hz, LH), 7.
65 (s, 2H)” CNMR (CD (/!3);
d 11.75 (q, J □ 1.4 Hz).

29.6 (q, J = 2.5 H2), 37.
28 (q.

' J = 2.0 Hz), 41.02 (q, J
= 26.6 H2).

127.56 (q, J = 281.2 Hz)
, 175.02 (s), 176.03 (s
)”F NMR(CHzCjl!z); d7.
7 (d, J・9.8 Hz) Applicant Mitsubishi Kasei Corporation

Claims (1)

[Claims] (1) General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼…[I] [R^1 represents an alkyl group, A is -CH_2- or ▲There are mathematical formulas, chemical formulas, tables, etc.▼(R ^2 indicates an alkyl group), ▲There are mathematical formulas, chemical formulas, tables, etc.▼ indicates a 5-membered ring with an asymmetric carbon, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ indicates an asymmetric carbon show. ] An ester derivative represented by