CS223403B1 - method of making the intermediateproduct for preparation of the derivatives of the prostadien acid - Google Patents

Description

In the synthesis of prostaglandin derivatives utilizing the Coreylio pathways [EJ Corey Ann NY Acad. Sci., 180, 24 (1971)] is one of the key moments of the reduction of the "enone" resulting from the introduction of the ω-chain into. Horner molecules by the Emmons modification of the Wittig reaction. Kétonická ¹ skupina! The "enone" is on the future 15th carbon atom of the prostadienoic acid derivative. Upon further reduction, for example with sodium or zinc borohydride, a 1: 1 mixture of the 15 S and 15 R epimer is obtained as described for the synthesis of PGF ₂ '[EJ Corey et al., J. Am. Chem. Soc., 90, 3247 (1968) and F. Kienzle et al., J. Org. Chem., 38, 3440 (1973). Although some compounds can be reduced selectively at low temperatures by special hydrides [EJ Corey et al., J. Am. Chem. Soc., 94, 8646 (1972)], such as Selectride (diisobutyllithium borohydride), is the problem of utilizing the 15 R epimer of the so-called "enol" of formula I

The object ¹ vynálbzu je- · * method 'production dut lezítéHo intermediate ^1' for the preparation of biologically active · děriváíůt prostadienoic acid-like- ¹ "Errante ^'one of' formula ΙΓ ^> CH = CH-C" CH ₂ R

ORx O where R represents residue (II)

O

CH2CH2H2CH2R2

OR ₁ OH (I) where R and R 1 are as described above, remain very current as they represent the possibility of almost doubling the yield, which is particularly attractive for substances which are difficult to reduce selectively (e.g. "enones" of formula II), or if the reduction has little selectivity. A mixture of 15 S and 15 R epimers of "enol" can be separated chromatographically into the desired 15 S and undesired 15 R epimer.

The above-mentioned drawbacks are overcome by the process according to the invention, characterized in that the 15 R epimer of the "enol" of the general formula (I)

Δ δ & H

OR ₁ (1) wherein R represents a residue

whereas

X is halogen and n is an integer from 0 to 3,

R1 is —CO — R2, wherein R2 is phenyl substituted with phenyl, or phenylcarbamoyl, is preferably oxidized by a Jones reagent in acetone or other low-boiling ketone at temperatures of 223.2 to 273.2 K, preferably 253 to 263 K. The oxidation reaction produces the "enone" of formula II λ

C = J = ch-ch-ch ₂ rt

OR, O (II) wherein R and R 1 are as defined above, which are further reduced to a mixture of "enols".

Thus, all the 15 R epimer of the "enol" is also used in this procedure, which increases the overall yield of the synthesis twice.

Exemplary embodiment

To a solution of 3 g of the "enol" of the above formula I wherein R is m-chlorophenoxy and R 1 is p-phenylbenzoyl in 140 ml of acetone cooled to 253.2 K was added dropwise 2.5 ml of Jones reagent (0.58 g of chromium trioxide and 0.6 ml of sulfuric acid, supplemented with 2.5 ml of water) and, after addition, stirred for 30 minutes. The reaction was quenched by the addition of 0.2 mL of isopropyl alcohol, 50 mL of chloroform was added, and the chromium salts were removed by shaking with a saturated NaCl solution. The organic layer was dried over magnesium sulfate and the solvent was evaporated in vacuo. The crude product (97% yield) was purified by crystallization from a mixture of dichloromethane and ether. 2.76 g (92%) of the "enone" of the above general formula (II) with a melting point of 422.2 to 424.2 K were obtained. The identity of the substance was confirmed by mass spectrometry.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of intermediates for the preparation of a prostadienoic acid derivative, such as an "enone" of the general formula II wherein R is a radical wherein X is halogen and an integer of 0 to 3, R 1 is a group -CO-R 2. wherein the 15 R epimer of the "enol" of formula I AND y. • B STEED. CH-CH-CH-CH 2 R 2 OH (1) wherein R and R 1 are as defined above, are treated with Jones reagent in acetone at temperatures of 223.2 to 273.2 K, preferably at 253.2 to 263.2 K.