JPS6122049A - 3,4-hydroxybutanoic acid ester and its preparation - Google Patents

Abstract

NEW MATERIAL:3,4-Dihydroxybutanoic acid ester of formula I (R<1> is <=4C alkyl; R<2> is H or protected hydroxyl). EXAMPLE:3,4-Dihydroxybutanoic acid methyl ester. USE:Useful as a synthetic intermediate of various physiologically active compounds. For example, 3-hydroxy-4-butanolide having insect pheromone activity can be synthesized easily from the compound. PREPARATION:The compound of formula I can be prepared by reducing the compound of formula II with equimolar amount of borane dimethylsulfide complex or borane tetrahydrofuran complex in tetrahydrofuran in the presence of a catalytic amount of sodium tetrahydroborate or lithium tetrahydroborate.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 3,4-dihydroxybutanoic acid esters of the formula and compounds of the formula ( The present invention relates to a method for producing the compound of 1).

In formulas (1) and (n), R1 represents a lower alkyl group.

R2 represents a hydrogen atom or a hydroxyl group protected with a protective group.

- The above-mentioned 3,4-dividroxybutanoic acid ester is a useful compound that is recognized to have high utility value as a synthetic intermediate for various physiologically active fragrances. Especially α of the compound of formula (■)
- carbon and β-carbon are asymmetric carbons, so the formula (I
If an optically active form is prepared as the compound of formula (I), the compound of formula (1) can also be obtained as an optically active form, so the usefulness of the compound of formula (I) becomes even greater.

3.4-dihydroxybutanoic acid esters have not been synthesized to date. In the compound of formula (I), the compound in which R1 is a pentyl group and R2 is a hydrogen atom is only known as a compound having a structure most similar to the compound of formula (1) (C, A).

Brighton and D. Faulkner,
U, 3.2+ 595+ 636+1952).

In the present invention, the 3,4-dihydroxybutanoic acid esters are produced by a subsequent general step reaction operation.
Can be converted to 4-butanolide. It is already known that this compound is an important intermediate of insect pheromones;
A previously disclosed synthetic route for 3-hydrolex-4-butanolide required 7 steps from the compound of formula (I[) (K, Mori, T, Takigalla, a
nd T, Matsuo+ Tetrahedron
+35+933 (1979)). From this, it can be understood how important the compound of formula (I) is as a synthetic intermediate.

The present inventors recognized the importance of the above background and expressed the formula (■゛)
We conducted intensive studies to selectively reduce the alkoxycarbonyl group at the α-position of the compound of formula (1) to directly lead to the compound of formula (1).

As a result, when the compound of formula (II) is reduced in the coexistence of a molar equivalent of borane/dimethylsulfide complex or borane/tetrahydrofuran complex and a catalytic amount of sodium or lithium tetrahydroborate in tetrahydrofuran, the compound of formula (1) is obtained in good yield. The present inventors have discovered that the following can be obtained, and have completed the present invention.

A feature of the present invention is that the desired conversion can only be carried out by combining a borane complex and a catalytic amount of an alkali metal tetrahydroborate. actually,
When reduction is carried out using only the borane complex, more than 30% of the compound of formula (II) remains after 72 hours at room temperature, but when the above alkali metal salt is present, the reaction takes place within 1 hour at room temperature. has been completed. On the other hand, when the compound of formula (II) is reduced only with an alkali metal tetrahydroborate salt,
Consumption of the compound of formula (II) was completed in 2 hours at room temperature, but in this case, the formation of the compound of formula (I) could not be confirmed, giving a mixture with an unknown complex structure.

Next, examples of the present invention will be given.

Example 1 (19.4 g of 31-(-)-malic acid dimethyl ester
(0,120 mol) in tetrahydrofuran (250 mol)
7%) at room temperature with borane dimethyl sulfide complex 12.
．． Add 2-component (0,122 mol) and stir for about 3 minutes.

0.2 g (6 mmol) of sodium tetrahydroborate was quickly added to the mixture, and the mixture was stirred for 30 minutes at room temperature. Subsequently, 77 methanol was injected, and stirring was continued for 30 minutes at room temperature. The solvent and low boilers were removed under reduced pressure, and the resulting oil was purified with a silica gel column to obtain the desired 3, 14.1 g (88% yield) of methyl 4-dihydroxybutanoate is obtained.The structure of a part of this product was confirmed as a 3,4-〇-isopropylidene derivative.Structure of formula (I[[) The analytical values for the compound are shown below.

Mass spectrometry 159 (M-CHa); Optical rotation [
α〕12+8.62° (C5,01, Eton)
; Infrared absorption spectrum V (c = o) 174
5cm-'(film);"H-NMR spectrum (CDα8) 61.36 (3■, S)
, 1.41” (3B, S).

2.52 (IH, dd,, J = 15.7.6.8
Hz,CdanC00CR3).

2.71 (IH, dd, J = 15.7.6.4
Hz, C-HCooCHs).

3.70 (3H,S), 4.16 CIH
, dd, J = 8.3. 5.9 Example 2 Compound 6 obtained by protecting only one of the two hydroxyl groups of L-tartrate dimethyl ester with a tetrahydropyranyl group
5.8 ■ (0.2 jl mmol) of borane dimethyl sulfide complex 0 in a tetrahydrofuran solution (0.6 d)
．． 026d (0,258 mmol) was added, followed by 0.5 mm of sodium tetrahydroborate (approximately 5 mol %), and the mixture was stirred at room temperature for 1.5 hours. After injecting 0.18 parts of methanol into the reaction mixture and subsequently stirring for 30 minutes, the solvent was removed under reduced pressure and the resulting colorless oil was purified using a silica gel column (2S
, 3S) -3,4-dihydroxy-2-(2'-tetrahydropyranyloxy)methylbutanoate 37■(6
2% yield) is obtained. The product is methyl 3.4-0-isopropylidene-2-hydroxy-butanoate (IV
) and methyl 3.4-0-isopropylidene-2-acetoxybutanoate (V), and the structure was confirmed.

(■) (V) Analysis value for (IV) Mass spectrometry 175 (M-CHs); Optical rotation [α
Kan + 18.4° (C1,44,CBCI!s)
; Infrared absorption spectrum J/ (OH) 3500
V (c = o) 1745 cm-' (f
ilIl).

'H-, NMR spectrum for (V) (CDC1a
) δ1.36 (3H,S), 1.43 (3
B, S), 2.18 (3H, S).

Claims (3)

[Claims] (1) Formula, ▲Mathematical formula, chemical formula, table, etc.▼(I) (In the formula, R^1 is an alkyl group with 4 or less carbon atoms, R^2 is hydrogen or a hydroxyl group protected with a protecting group. 3,4-dihydroxybutanoic acid ester of (2) Formula, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) (In the formula, R^1 is a lower alkyl group with 4 or less carbon atoms, R^
2 represents hydrogen or a hydroxyl group protected with a protecting group) ▲Mathematical formula, chemical formula,
There are tables, etc.▼(I) Method for producing 3,4-dihydroxybutanoic acid esters (the symbols in the formula are the same as above). (3) The method of item 2, wherein a combination of a borane complex and a catalytic amount of an alkali metal tetrahydroborate is used as the reducing agent.