CS209013B1 - Process for preparing 4-formyl-4-allylpimelic acid esters - Google Patents

Abstract

4-Formyl-4-allylpimelic acid esters of the general formula I, in which Ø denotes alkyl with 1 to 4 carbon atoms, are intermediates in the manufacture of pharmaceuticals. They can be prepared by the addition of the corresponding acrylic acid esters to 4-pentenal enamines of the general formula II, where R1 and R2 are the same or different alkyls with 3 to 5 carbon atoms or R1 and R2 form a polymethylene chain with 4 to 5 carbon atoms in polar organic solvents.

Description

4-Formyl-4-allylpimelic acid esters of formula I

CHO

AND

R-OCO-CH ₂ -CH ₂ -C-CH ₂ -CH ₂ -COO-R

AND

CH ₂ -CH = CH ₂ (I) in which R represents C 1 -C 4 alkyl are intermediates in the manufacture of medicaments. They can be prepared by addition of the appropriate acrylic esters to the 4-pentenal enamines of the general formula Π,

N-CH = CH-CH ₂ -CH 2 CH ₂

R ² (Π) ii

wherein R ¹ and R ² are the same or different alkyl of 3 to 5 carbon atoms or R ¹ and R ² form a polymethylene chain of 4 to 5 carbon atoms in polar organic solvents.

209 013

The present invention relates to a process for the preparation of 4-formyl-4-allylpimelic esters of the general formula I:

CHO i

r-oco-ch ₂ -ch ₂ -c-ch ₂ -ch ₂ -coo-r

AND

CH ₂ -CH = CH _{2 -} (I) wherein R is C 1 -C 4 alkyl.

Substances of this type are novel and are intermediates in the pharmaceutical industry.

The process according to the invention is characterized in that the amines of the general formula II

K ¹ (II) n-ch = ch ₂ -ch = ch ₂

R ² in which either R ¹ and R ² 'denotes the same or different) alkyl of 3 to 5 carbon atoms, or R ¹ + R ² forms a polymethylene chain of 4 or 5 carbon atoms, add esters of acrylic acid of formula III, ch ₂ = ch-coo-r (m) where R has the same meaning as above, in the presence of. '! of a polar organic solvent at a temperature of from -10 ° C to the boiling point of the mixture. |

The addition is carried out in protic or aprotic solvents, e.g. methanol, ethanol or acetonitrile.

The addition may be carried out such that the reaction components are slowly mixed at -10 C.až ^e at room temperature and then the reaction mixture maintained at elevated temperature, preferably at reflux temperature.

In the process according to the invention, a stoichiometric amount, but more preferably an excess of the ester of the general formula, is used for the addition

III.

The following examples illustrate but do not limit the generality of the process of the invention.

Example 1

Dimethyl 4-formyl-4-allylpimelate (I, R denotes CH ₃ )

To a stirred solution of 345.5 g (4.013 mol) of methyl acrylate (III, R = CH ₃ ) in 1000 ml of methanol was added dropwise at -5 ° C under nitrogen over 40 minutes 172 g (1.2535 mol) of 1- (1). (4-pentadien-1-yl) pyrrolidine (II, R ¹ + R ^{2 '} together is - CH ₂ - (CH ₂ ) ₂ --CH ₂ -). The reaction mixture is allowed to warm to room temperature, heated to boiling for 30 h and then concentrated to;

Also rotary evaporator under reduced pressure. Evaporate ^! shake for 10 minutes with a mixture of 800 ml of 13% hydrochloric acid and 800 ml of methylene chloride; the separated aqueous phase is extracted again with 150 ml of methylene chloride. The combined organic solutions were washed with 200 ml 7% hydrochloric acid, 2 x 200 ml water and dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue is distilled in an oil pump vacuum and 185.6 g of dimethyl-4-formyl-4-allylpent (1, R = CH ₃ ), corresponding to 57.8% tec, are obtained. temperature ⁺ boiling in the range of 134 to 135.5 ° C at 25 mmHg.

Example 2 __ ..

Dibutyl-4-formyl-4-allylpimelate (I, R 1 = CH ₃ (CH ₂ ) ₃ ) "

To a stirred solution of 20.9 g (0.1 mol) of N-ia-butyl-N-pentylamine (Π, R ¹ is (CH 3) ² CHCH ₂ , R ² is CH 3 (CH ₂ ) ₃ CH ₂ ) in 200 ml of acetonitrile is added dropwise. at 10 ° C 51.2 g (0.4 mol) of butylacrylate (ΠΙ, FK means CH ₃ (CH ₂ ) ₂ CH ₂ ) over 30 minutes and the mixture is then heated to boiling for 45 h. After cooling, the aqueous phase ^{1 was} separated and extracted twice with 45 ml of benzene. The combined / organic phases are washed with 40 ml of 3% hydrochloric acid

- and 2x 50 ml of water. After drying over anhydrous magnesium sulfate, the solution was evaporated on a rotary evaporator. The residue was distilled under vacuum ^. vacuum pump, yielding 14.4 g (42.3%) of dibutyl-4-formyl-4-allylpimelate (I, R = CH ₃ (CH 2) ₂ CH ₃ ). The temperature warns 159-164 ° C at 14 Pa. '

Claims (2)

SUBJECT OF THE INVENTION A process for the preparation of 4-formyl-4allylpimelic esters of the general formula I, CHO ί R-OCO_CH ₂ -CH ₂ -C -CH ₂ -CH ₂ -COO-R, CH ₂ -CH = CtÍ2 (I) in which R represents alkyl having 1 to 4 carbon atoms, characterized in that enamines of the general formula II R ¹ . R ² N-CH = CH-CH ₂ -CH = CH ₂ (Π) in which either R ¹ and R ² denote the same by different C 3 -C 5 alkyls or R ¹ + R ² form a poly (4 or 5 carbon polymethylene chain) The acrylic acid esters of the general formula (III) are added CH ₂ = CH-COO-R (ΠΙ) where R has the same meaning as above, in the presence of a polar organic solvent at a temperature from -10 ° C to the boiling point of the mixture. 2. Process according to claim 1, characterized in that the addition is carried out in a protic or aprotic solvent, preferably methanol, ethanol or acetonitrile.