CS208913B1 - Manufacturing process of (+)-2-amino-1-butanol by cleavage of racemic aminobutanol - Google Patents

Description

(54) A method for producing (+) - 2-amino-1-butanol by cleavage of racemic aminobutanol

The present invention relates to a process for the preparation of optically active (+) - 2-amino-1-butanol by resolution of racemic 2-amino-1-butanol with L - (+) - mandelic acid.

L - (+) - 2-Amino-1-butanol is a valuable intermediate in the synthesis of certain pharmaceutically important compounds, such as D-lysergic acid (+) - 1-hydroxy-2-butylamide (methylergobasine).

The literature (FH Radke, RB Fearing and SW Fox: J. Am. Chem. Soc. 76, 2801 (1954)) describes a process for preparing (+) - 2-amino-1-butanol by cleavage of racemic 2-amino-1- butanol with L-glutamic acid. However, the overall yield of optically active (+) - 2-amino-1-butanol is low (about 50% based on the (-1) - enantiomer contained in the racemate). A further disadvantage of this process is the difficult and low recovery recovery of the L-glutamic acid used, which further reduces the economics of the process, especially in the preparation of larger quantities of the optically active amino alcohol.

According to the invention, L - (+) - 2-amino-1-butanol is prepared in very good yield by cleaving racemic 2-amino-1-butanol with L - (+) mandelic acid in ethanol and decomposing the precipitated L - (+) - mandelate Of (+) - 2-amino-1-butanol with a strong base, preferably sodium ethylate, in an environment of industrial absolute ethanol.

Cleavage of racemic aminobutanol with L - (+) - mandelic acid is preferably carried out in ethanol, especially since in this medium L - (+) - mandelate is (+) - 2-aminobutanol, unlike the same salt of (-) - 2- amino-1-butanol, very poorly soluble: it precipitates almost quantitatively from solution and is optically uniform after one crystallization from the same solvent.

Similarly, the use of a sodium equivalent of sodium ethylate to decompose (+) - 2-amino-1-butanol L - (+) - mandelate in absolute technical ethanol is similarly expedient because of the very limited solubility of the resulting sodium salt of L - (+) - man > debt in said solvent. This procedure provides (+) - 2-amino-1-butanol in a yield of up to 30% higher than the literature cited for the decomposition of a similar salt of L-glutamic acid.

A further advantage of the process of the invention is that the L - (+) - mandelic acid used is readily accessible (see R. Roger: J. Chem. Soc. 1935, 1544) and can be regenerated easily and in high yield after cleavage. used again for cleavage.

Further details of the process according to the invention are given in the example below; in the example, temperatures are given in ° C, and all aminobutanol base operations are performed under a nitrogen atmosphere.

Exemplary embodiment

To a solution of 912 g of L - (+) - mandelic acid in 900 ml of ethanol at 40-45 ° under stirring is added a solution of 534 g of racemic 2-amino-1-butanol in 300 ml of ethanol and the reaction mixture is left to crystallize overnight. at 0 - 1-5 °. The precipitated aminoalcohol salt is filtered off, washed with ethanol and, after drying in air at room temperature, recrystallized from boiling ethanol. 660 g of pure L - (+) - mandelate (+) - 2-amino-1-butanol of 1.130-133 ° and an optical rotation of (a) n ° + 77 ± 1 ° (c = 0.5, water) are obtained. .

To a solution of 650 g of L - (+) - mandelate (+) - 2-amino-1-butanol in 3200 ml of ethanol at 50 ° is added a solution of sodium ethylate obtained by dissolution

61.8 g of sodium in 1300 ml of ethanol. The reaction mixture, in which the colorless sodium mandelate precipitates, is cooled to 30 ° and slowly diluted with a total of 4550 ml of anhydrous ether. The mixture was allowed to stand overnight at room temperature

0-5 °, then the precipitated salt is filtered off and washed with ether which is collected separately. From the bulk of the filtrate, solvents were distilled off through a 60 cm Vigreux column; After concentrating to a volume of about 1000 ml, the concentrate was diluted with washing ether, allowed to stand overnight at 0-5 ° and the next day a small amount of precipitated sodium mandelate (20 g) was filtered off and washed with ether. After distilling off the solvents from the combined filtrates, the crude aminobutanol was distilled off under a water pump vacuum through a 25 cm long loose-packed column. 240 g of (+) - 2-amino-1-butanol having a bp of 80-85 ° (1599.86 Pa) and an optical rotation (?) Of _D ²⁰ + 9.8 ° (for undiluted substance) are obtained.

The filtered sodium mandelate and L - (+) - mandelate (-) - 2-amino-1-butanol, which is eliminated from the resolution of racemic aminobutanol, are dissolved in water and L - (+) - mandelic acid is released from the solution with hydrochloric acid. shake into ether. After evaporation of the solvent, the crude regenerated acid is recrystallized from acetone / benzene. 875 g of pure L - (+) mandelic acid having a melting point of 131-133 ° and an optical rotation of (α) _D ²⁰ + 152 ° ± 4 ° (c = 2.9, water) are obtained.

Claims (1)

SUBJECT OF THE INVENTION Process for the preparation of (+) - 2-amino-1-butanol by cleavage of racemic aminobutanol, characterized in that the cleavage is carried out with L - (+) - mandelic acid in ethanol and then from the precipitated L - (+) - mandelate (+) The 2-amino-1-butanol by decomposition with a strong base, preferably sodium ethylate, liberates the optically active amino alcohol in ethanol, which is isolated by distillation.