Process for preparing optically active 6-t-butyoxy-3,5-dihydroxyhexanoic esters

• US 4,994,602 A
• Filed: 02/27/1990
• Issued: 02/19/1991
• Est. Priority Date: 02/27/1989
• Status: Expired due to Term

• Current Assignee: Takasago International Corporation
• Original Assignee: Takasago International Corporation
• Inventors: Sayo, Noboru, Kumobayashi, Hidenori, Seido, Nobuo
• Primary Examiner(s): Killos, Paul J.
• Application Number:
  US07/485,692
• Time in Patent Office: 357 Days
• Field of Search: 560/186
• US Class Current: 560/186
• CPC Class Codes: C07C 67/31 by introduction of functional groups containing oxygen only in singly bound form
• CPC Class Codes: C07C 69/708 Ethers

Abstract

A process for preparing an optically active 6-t-butoxy-3,5-dihydroxyhexanoic ester represented by formula: ##STR1## wherein t-Bu represents a t-butyl group; and R⁴ represents a lower alkyl group, which is useful as a precursor of a lactone moiety of campactin, mevinolin or analogues thereof is disclosed, comprising asymmetrically hydrogenating a 4-t-butoxyacetoacetic ester in the presence of a ruthenium-optically active phosphine complex to obtain an optically active 4-t-butyoxy-3-hydroxybutanoic ester, reacting the ester with a lithium enolate of an acetic ester to obtain an optically active 6-t-butyoxy-5-hydroxy-3-oxohexanoic ester, and asymmetrically hydrogenating the resulting ester in the presence of a ruthenium-optically active phosphine complex as a catalyst. The desired product can be obtained in good yield at high stereoselectivity.

Claims

1. A process for preparing an optically active 6-t-butoxy-3,5-dihydroxyhexanoic ester represented by formula (VII):

##STR7## wherein t-Bu represents a t-butyl group; and

R⁴ represents a lower alkyl group, comprising asymmetrically hydrogenating a 4-t-butoxyacetoacetic ester represented by formula (I);

##STR8## wherein t-Bu is as defined above; and

R¹ represents a lower alkyl group, in the presence of a ruthenium-optically active phosphine complex represented by formula (II);

space="preserve" listing-type="equation">Ru(R.sup.2 --BINAP)(O.sub.2 CR.sup.3).sub.2 (II)

wherein R² -BINAP represents a tertiary phosphine represented by formula (III);

##STR9## wherein R² represents a hydrogen atom or a methyl group; and

R³ represents a lower alkyl group or a trifluoromethyl group, to obtain an optically active 4-t-butoxy-3-hydroxybutanoic ester represented by formula (IV);

##STR10## wherein t-Bu and R¹ are as defined above, reacting the compound represented by formula (IV) with a lithium enolate of an acetic ester to obtain an optically active 6-t-butoxy-5-hydroxy-3-oxohexanoic ester represented by formula (V);

##STR11## wherein t-Bu and R⁴ are as defined above, and then subjecting the compound represented by formula (V) to asymmetric hydrogenation using a ruthenium-optically active phosphine complex represented by formula (VI);

space="preserve" listing-type="equation">Ru.sub.2 Cl.sub.4 (R.sup.2 --BINAP).sub.2 (NEt.sub.3) (VI)

wherein R² -BINAP is as defined above; and

Et represents an ethyl group, as a catalyst.

2. A process as in claim 1, wherein in the asymmetric hydrogenation of the 4-t-butoxyacetoacetic ester of formula (I), the ruthenium-optically active phosphine complex of formula (II) is used in an amount of from 0.001 to 0.1 mole per mole of the 4-t-butoxyacetoacetic ester of formula (I).

3. A process as in claim 2, wherein in the asymmetric hydrogenation of the 4-t-butoxyacetoacetic ester of formula (I), the ruthenium-optically active phosphine complex of formula (II) is used in an amount of from 0.002 to 0.01 mole per mole of the 4-t-butoxyacetoacetic ester of formula (I).

4. A process as in claim 1, wherein the asymmetric hydrogenation of the 4-t-butoxyacetoacetic ester of formula (I) is conducted at a temperature of from 25°

to 100°

C. under a hydrogen pressure of from 5 to 150 kg/cm².

5. A process as in claim 4, wherein the hydrogen pressure is from 30 to 70 kg/cm².

6. A process as in claim 1, wherein the reaction of the optically active 4-t-butoxy-3-hydroxybutanoic ester of formula (IV) is with the lithium enolate of acetic ester and is conducted in tetrahydrofuran at a temperature of -50°

C.

7. A process as in claim 1, wherein in the asymmetric hydrogenation of the optically active 6-t-butoxy-5-hydroxy-3-oxohexanoic ester, the ruthenium-optically active phosphine complex of formula (VI) is used in an amount of from 0.001 to 0.1 mole per mole of the optically active 6-t-butoxy-5-hydroxy-3-oxohexanoic ester.

8. A process as in claim 7, wherein in the asymmetric hydrogenation of the optically active 6-t-butoxy-5-hydroxy-3-oxohexanoic ester, the ruthenium-optically active phosphine complex of formula (VI) is used in an amount of from 0.002 to 0.01 mole per mole of the optically active 6-t-butoxy-5-hydroxy-3-oxohexanoic ester.

9. A process as in claim 9, wherein the asymmetric hydrogenation of the optically active 6-t-butoxy-5-hydroxy-3-oxohexanoic ester is conducted at a temperature of from 5°

to 100°

C. under a hydrogen pressure of from 10 to 120 kg/cm².

10. A process as in claim 9, wherein the asymmetric hydrogenation of the optically active 6-t-butoxy-5-hydroxy-3-oxohexanoic ester is conducted at a temperature of from 30°

to 50°

C. under a hydrogen pressure of from 50 to 100 kg/cm².