CS213293B1 - Process for the preparation of D- (5R, 8R, 10R) -6-methyl-8- (1,2-dihydroxyethylergelin) - Google Patents

Abstract

The invention relates to a method for the production of D-(5R, 8R, 10R)-6-methyl-8-(1,2-dihydroxyethyl) ergoline, consisting in the reduction of the ketone carbenyl group and the simultaneous reduction of the masked aldehyde function in 1-(D-(5R, 8R, 10R)-6-methyl-8-ergolineyl)-3-(methylthio)-3-(acetoxy)acetone to alcoholic functions. The reduction is carried out by the action of sodium borohydride from 0°C to the boiling point of the reaction mixture.

Description

The present invention relates to a process for the preparation of D- (5R, 8R, 10R) -6-methyl-8- (1,2-dihydroxyethyl) ergoline

/ 1 /.

which is an intermediate in the synthesis of biologically active partially synthetic derivatives of natural ergot alkaloids. Although the compound of Formula I did not show significant efficacy in biological screening (antinidative and antilactant activity); however, it is a valuable intermediate for modifying substituents in position 8 of the ergoline backbone and for the synthesis of substances structurally related to D-6-methyl-8-ergolinylacetamide (Semonský M. et al., Cellection Czech.Chem.Commun. 36, 2200 (1971), respectively. nicergoline (Bernardi L .: Arzneimitel.-Forsch./Drug.Res/ 29, (8a), 1204 (1979)), all of which have remarkable biological activity.

According to the invention, the compound of formula I can be prepared from a compound of formula II

OCOCH 3 (11), by reduction with sodium borohydride in a lower alcohol, preferably methanol, at a temperature of 0 ° C to 0 ° C.

A to the boiling point of the reaction mixture, preferably at a temperature of 20 to 25 ° C,

The reaction of II with sodium borohydride consists in reducing the carbonyl group of the ketone to the hydroxy derivative, while reducing the masked aldehyde function. Other complex hydride reduction processes, such as lithium aluminum hydride in tetrahydrofuran or 1,2-dimethoxyethane, or sodium dihydro-bis (2-methoxyethoxy) aluminate in benzene, alkali metal reduction in boiling alcohol, can also be used for this purpose, or reduction of metals in an acidic medium. However, these methods have certain disadvantages in terms of the preparation and conduct of the reaction, as well as the isolation and purity of the end product, over the simplicity of the process of the present invention.

The compound of formula (II) used as a starting material is a substance known and readily prepared according to our U.S. Pat. copyright certificate.

Further details of the process for the preparation of the compound of formula 1 will be apparent from the following non-limiting example.

Example 1

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To a solution of 3.72 g (10 mmol) of 1- [D- (5R, 8R, 10R) -6-ethyl-8-ergelinyl] -3- (methilthyl) -3] acetexy] acetene in 150 ml of methanol is added in small portions over 3 ▼ hed 7.6 g (0.2 mole) of natriumberehydridu and the reaction mixture was stirred at room temp for 20 to 25 ^e C 6 PE Debu Hedin, then allowed to stand at the same temp an additional 12 Hedin. To quench the reaction mixture with water, the reaction product is taken up in chloroform and, after drying over anhydrous sodium sulfate and evaporated to dryness, the reaction product is purified by silica gel column chromatography. Elution with chloroform first with about 20% ethanol and then with 50 vol% ethanol yielded pure material which was recrystallized from ethanol to give compound e heat mp 240-242 * C / tf _r ²⁰ = - 112.5 (c = 0.343, pyridine).

Claims (1)

BACKGROUND OF THE INVENTION characterized in that the compound of formula II is reacted with sodium hydride in a lower alcohol, preferably methanol, at a temperature of about 0 ^° C to the boiling point of the reaction mixture, preferably at a temperature of 20 to 25 ° C.