DE1939697B2 - Aminol hol esters and agents containing them - Google Patents

Description

have a choleretic effect, which is all the more surprising as there is no known choleretic Agent derived from amino alcohols.

The claimed compounds can be obtained by condensation of acid halides of the formula

(CH = CH) _n - COX

with amino alcohols of the formula

HO —CHj —CH, -N

R »

getting produced. In these formulas, X is a halogen, while the other members are the same as above Have meanings. This condensation becomes beneficial: in a non-polar solvent such as benzene with agitation and exclusion of moisture at ambient temperature with stoichiometric amounts the respondent carried out. Generally the reaction will take 12 to 24 hours at ambient temperature or carried out under reflux for a few hours. The preparation of some compounds of the formula (I) is described in the following examples.

example 1
Hydrochloride of 2-morpholinoethyl-O-acetyl-

vanillate
η = O; NR ¹ R * = morpholino

In a 250 ml three-necked flask with a reflux condenser with attached calcium chloride tube, Dropping funnel and a mechanical stirrer is seen, a solution of 13.7 g (0.06 mol) O-acetylvanilloyl chloride in 50 ml of anhydrous benzene given. A solution of 7.9 g (0.06 mol) is gradually added through the dropping funnel with stirring. 2-morpholinoethanol in 35 ml of anhydrous benzene was added. The mixture is then refluxed for 6 hours and the solution is then cooled. The departed Crystals are suction filtered and dried. Here, 14 g of impure hydrochloride of 2-morpholinoethyl-O-acetylvanillate obtain.

After dissolving in water, it is made with sodium bicarbonate made alkaline and the base extracted with ether. The solvent is evaporated, whereby 9.4 g of the light yellow oily base remain, the

is converted into the hydrochloride by adding the calculated amount of anhydrous hydrochloric acid dissolved in ether. After filtering off with suction, washing with ether and drying, 10.2 g of the crude hydrochloride with a melting point of 160 ^° C. are obtained. After recrystalline

sation of 500 ml of acetone, to which 50 ml of ether are added, the hydrochloride melts at 161 g corresponding to 36% yield ⁰ C. 7.8. The compound is slightly hygroscopic and soluble in about 5 parts of water.

Elemental analysis for C ₁₆ H ₈ SClNOg:

Calculated ... C 53.40, H 6.46, Cl 9.85, N 3.89%; Found ... C 53.27, H 6.20, Cl 9.92, N 3.96%.

Example 2

Hydrochloride of 2-dimethylaminoethyl-O-acetylvanillate

η = 0; R ¹ = R * = methyl

The experiment is carried out in the manner described in Example 1, but using 5.35 g (0.06 mol) of 2-dimethylaminoethanol instead of 7.9 g of 2-morpholinoethanol. The crude hydrochloride is recrystallized from an acetone / ethyl acetate mixture (1: 2). 7.8 g (yield 41%) of a highly hygroscopic, easily water-soluble product with a melting point of 100 to 105 ^° C. are obtained here. Elemental analysis for C ₁₄ H _{20 ClNO 5} : Calculated ... C 52.91, H 6.30, Cl 11.17, N4, n% _: found ... C 52.70, H 6.15, Cl 1L20, N 4.18%.

Example 3

Hydrochloride of 2-piperidinoethyl-O-acety] vanulate

π = 0; NR ¹ R * = piperidino

The experiment is carried out in the manner described in Example 1, but using 7.75 g (0.06 Mo!) «5 of 2-piperidinoethanol instead of 7.9 g of 2-morphiiolinoethanol. After recrystallization from acetone-ether (8: 1) and a second recrystallization from acetone, 9.2 g (yield 43%) of the slightly hygroscopic hydrochloride, which is soluble in about 10 parts of water and has a melting point of 169 ° C., is obtained.
Elemental analysis for C ₁₇ H _{24 -ClNO 5} :

Calculated ... C 57.05, H 6.76, Cl 9.90, N 3.91%; Found ... C 56.99, H 6.82, Cl 9.88, N 4.25%.

Example 4

Hydrochloride of 2-diisopropylaminoethyl-O-acetylvanillate

/ i = 0; Ri = R ² = isopropyl

The experiment is carried out in the manner described in Example 1, but using 8.7 g (0.06 mol.) 2-diisopropylaminoethanol instead of 7.9 g of 2-morpholinoethanol carried out. After recrystallization from ethyl methyl ketone, 14.4 g (yield 64%) of the slightly hygroscopic hydrochloride, which is soluble in about 4 parts of water and has a melting point of 163 ° C.

ditched. After adding 300 ml of petroleum ether, the mixture is left to stand for 2 hours. The crystals are suction filtered and dried in a desiccator. This gives 16.5 g of crude hydrochloride of 2-morpho-aminoethyl-O-acetylferulate. After recrystallization from 600 ml of ethanol, 13.3 g (57% yield) of the non-hygroscopic hydrochloride, which is soluble in about 20 parts of water and melts at 206 ° C., is obtained. Elemental analysis for C ₁₈ HmCINO ₆ : Calculated ... Cl 9.19%;

found ... Cl 9.03%.

Example 6

Hydrochloride of 2-dimethylaminoethyl-O-acetyl ferulate

" =

= R2 = methyl

^s °

B e i s ρ i e 1 5

2-Moφholinoäthyl-O-acetylferulat-hydΓOchlorid]

η = 1; NR ¹ R ² = morpho

A solution of 7.9 g (0.06 mol) of 2-morpholinoethanol in 25 ml of anhydrous benzene is placed in a 1000 ml three-necked flask equipped with a reflux condenser with attached calcium chloride tube, a dropping funnel and a mechanical stirrer. A solution of 15.3 g (0.06 mol) of O-acetylferuloyl chloride in 475 ml of anhydrous benzene is gradually added through the dropping funnel with stirring. The mixture is stirred for a further 3 hours at room temperature and overnight. The experiment is carried out in the manner described in Example 5, but using 5.35 g (0.06 mol) of 2-dimethylaminoethanol instead of 7.9 g of 2-morpholinoethanol . The crude hydrochloride is recrystallized from isopropanol which has been added to the ether. This gives 14.8 g (72% yield) of the hygroscopic hydrochloride which is very readily soluble in water and which instantly melts at 136.degree.
Elemental analysis for CIgH ₂₂ ClNO ₅ : Calculated ... N 4.07, Cl 10.3%; found ... N 3.81, Cl 10.35%.

Example 7

Hydrochloride of 2-piperidinoethyl-O-acetylferulate n = 1; NR ¹ R ² = piperidino

The experiment is carried out in the manner described in Example 5 using 7.75 g (0.06 mol) of 2-piperidinoethanol instead of 7.9 g of 2-morpholinoethanol. The crude hydrochloride is recrystallized from 1150 ml of acetone to which 150 ml of ether have been added. This gives 15.8 g (68% yield) of the non-hydroscopic hydrochloride, which is soluble in 5 parts of water and has a melting point of 168 ° C.
Elemental analysis for C ₁₈ H _{28 ClNO 5} : Calculated ... Cl9.23%;

found ... Cl9.20%.

Example 8

Hydrochloride of 2-diisopropylaminoethyl-O-acetylferulate

η = 1; R ¹ = R ² = isopropyl

The experiment is carried out in the manner described in Example 6 using 8.7 g (0.06 mol) of 2-diisopropylaminoethanol instead of 7.9 g of 2-morpholinoethanol. The crude hydrochloride is recrystallized twice from ethyl acetate. Here, 8.6 g (yield 36%) of the non-hygroscopic, water-soluble hydrochloride of melting point 14O ⁰ C.

Elemental analysis for C ₂₀ Hs _{0 CINO 5} :

Calculated ... C 60.06, H 7.56, Cl 8.86%; Found ... C 60.53, H 7.58, Cl 8.77%.

Claims (2)

697 claims: 1. Amino alcohol esters of the formula OCH, CH ₈ -CO-O , R ^x (CH = CH) _n - COO - CHj - CH ₂ - N: in which π = O or 1 and R ^x and R * both denote the methyl or isopropyl radical or, together with the nitrogen atom to which they are bonded, form the piperidino or morpholino group and their acid addition salts. 2. Medicinal product, consisting of a therapeutically safe carrier and an amino alcohol ester according to claim 1. The invention relates to amino alcohol esters of the formula OCH ₈ CH ₈ - CO - O - (CH = CH) _n - COO - CH _S - CH ₂ - N in which η = O or 1 and R ¹ and R ² both denote the methyl or isopropyl radical or, together with the nitrogen atom to which they are bonded, form the piperidino or morpholino group and their acid addition salts. It has been found that the compounds (I) a OCH, CH ₃ -CO-O- 'R *