CH650772A5 - METHOD FOR PRODUCING PYRROLIDIN-2-ONES FROM 3-PYRROLIN-2-ONES AND METHOD FOR PRODUCING THE 3-PYRROLIN-2-ONES. - Google Patents

Description

According to the present invention, optically active pyrrolidin-2-ones of the formula I are now optionally:

in which R1, R3, R4, R5 and R5 'have the same meaning as above 3s, optionally using a suitable catalyst, optionally an optically active catalyst [Angew. Chem. 83.956 (1971)] or a built-in asymmetric center of C-5 in the compound of formula V during the hydrogenation.

40 One of the main difficulties in the preparation of the pyrrolidin-2-ones of the formula I by hydrogenation of 3-pyrrolin-2-ones of the formula V is the difficulty in preparing the 3-pyrrolin-2-ones of the formula V. . The present invention therefore also encompasses general processes for the preparation of the compounds of the formula V, and this is carried out according to the present invention by ring closure of compounds of the formula IV:

(IV)

(I-C sharp)

to form the corresponding compound of formula V. This ring closure takes place according to the invention under basic conditions, e.g. in t-butanol with potassium t-butoxide as base under a nitrogen atmosphere, followed by acidification with a mineral acid, e.g. HCl, and dilution with water, or by ring closure of the corresponding

650772

Phosphonium bromides of the formula XIII:

PPhjBr

G

Aroyl = aryl-CO-alkanoyl = alkyl (minus 1 C) -CO-aryl = aromatic radicals, such as phenyl or naphthyl, heteroaromatic radical = aryl radical with a heteroatom s from the group pyridyl, furyl, thienyl, and the corresponding benzo derivatives, such as N-alkyl or N-aryl pyrrolyl, quinolyl, etc.

Alkyl = hydrocarbon radicals with preferably 1 to 16 [XIII] carbon atoms. These radicals can carry up to five identical or different substituents, e.g. Alkyl, halogeno-alkyl (e.g. F3C), O-alkyl, N-dialkyl (same or different alkyl groups), S-alkyl, halogen, O-benzyl, N-dibenzyl, N-alkyl / benzyl, S-benzyl, O- Aryl, S-aryl, N-diaryl, N-alkyl / benzyl / aryl, OH, nh2, SH, the 15 three latter groups being protected during the basic ring closure.

wherein the ring closure takes place in the basic medium to the corresponding compound of formula V.

In the present description, the terms used have the following meaning:

Certain 3-pyrrolidin-2-ones of formula V are claimed in U.S. Patent 3,272,842 and are obtained according to the following 20 equation:

R

\

C = 0 CH2-R3

[V]

However, R5 and R5 'exclude hydrogen and R4 is always S-ci12- (S = substituent). This ring closure of the compound of formula IV with R4 = aryl or substituted aryl and R5 and / or R5 'is hydrogen according to the examples of US Pat. No. 3,272,842 either does not take place or gives yellow compounds (probably dimers), which is due to the

Difference in the substituents, i.e. these known methods were not applicable to the present starting compounds.

3-Pyrrolin-2-ones of formula V have already been prepared by G. Stork and R. Matthews, Chemical Communications 1970, 445-6, according to the following reaction sequence:

R

OR

X

Ri. [^ 0R C

r5X \

r nnh.

R3 / ° Et

\ / P ° \

CH OEt

1) DCC

2) H +

(VI)

(VII)

5

650772

OEt

OEt

Close

DME

However, the use of dicyclohexylcarbodiimide (DCC) for the condensation of the aminoketone derivative of the formula VI with the unstable phosphonoacetic acid (formula VII) is unsuitable for large-scale syntheses. In addition, the price of DCC is very high, and N, N'-dicyclohexylurea is formed as a by-product, which is difficult to remove and makes the process even more uneconomical.

A similar ring closure reaction was described by T. W. Gun-20 tert et al. in Helv. Chim. Acta, 60, 334-9 (1977), which can be represented as follows:

CV)

However, this process requires repeated chromatographic separation for the isolation of the 3-pyrrolin-2-one of the formula V with R4 = 17β-steroidyl in 10% yield, so that this process is also unsuitable for production on an industrial scale. In addition, the authors were unable to produce the ring compound of the compound of formula IX (corresponding to the present compound of formula XII).

According to the present invention, the direct ring closure of the compounds of the formula IV is successfully carried out and even very conveniently used for the synthesis of substituted 3-pyrrolin-2-ones of the formula V, in particular if the substituents R 'and R3 of the compound of the formula IV meet the following two conditions: (1) Either R1 ^ H, ie R1 = alkyl, substituted alkyl, aryl, substituted aryl, alkanoyl or aroyl, or (2) when R1 = H, R3 is a group which stabilizes anions on the C-3 atom and is stable towards bases, i.e. Aryl, substituted aryl, alkanoylalkyl, etc., but not non-activating alkyl or hydrogen.

In particular for the preparation of compounds of the formula V by ring closure in the case where R1 = hydrogen and R3 = hydrogen, alkyl or substituted alkyl, it has been found that the following reaction sequence is best used. If R4 = aryl, substituted aryl, R5 = hydrogen, alkyl or substituted alkyl and R5 '= hydrogen, alkyl or substituted alkyl, it is possible to use 2-amino-acetophenone of the formula:

.4

(XI)

HCl

55 with a 2-bromoacyl chloride or bromide to give the corresponding bromine compound of the formula XII:

4th

60 R

(XII)

650772

to form in virtually quantitative yield. The bromine compound of formula XII, in contrast to the chlorine compound of formula IX, reacts with triphenylphosphine, e.g. in benzene or chlorobenzene solution, without decomposition to form the corresponding phosphonium bromide of the formula XIII:

R:

R

N

I.

H

which is sufficiently soluble in alcohols and water for the ring closure to the corresponding compound of formula V, e.g. with 2N NaOH solution.

According to this method, in particular the starting aminoketones of the formula XI, in which R4 = aryl, substituted aryl, alkyl or substituted alkyl, R5 = hydrogen, alkyl or substituted alkyl and R5 '= hydrogen or alkyl, are generally readily accessible compounds which in practically quantitative yield in weakly basic media, e.g. Sodium bicarbonate in a water-ether mixture, with 2-bromoacyl chlorides or bromides to give the corresponding N- (2-bromoacyl) aminoketone of formula XII, in which R3 = hydrogen, aryl, substituted aryl, alkyl or substituted alk'yl , can be acylated.

The ketones of formula XII react with triphenylphosphine, e.g. in benzene solution to form the corresponding phosphonium bromide of formula XIII, which precipitates and can be collected by simple filtration. In particular, dissolving the compound of formula XIII in alcohol (preferably methanol) or water and treating it with preferably more than one equivalent of the base (preferably 2N NaOH solution) in general at room temperature quickly forms the desired 3-pyrrolin-2-one Formula V and triphenylphosphine oxide in practically quantitative yield, which precipitates out of the solution. After dilution with water and evaporation of the alcohol, the mixture is collected and separated by extraction, e.g. with methylene chloride, which removes the triphenylphosphine oxide.

The 3-pyrrolin-2-one of formula V, which has been obtained by one of the above-mentioned methods, can easily be mixed with e.g. Pd / C, Pt or chiral rhodium complexes as a catalyst in an alcohol (preferably methanol) solution to the CNS-active substituted pyrrolidin-2-ones (formula I-cis) are hydrogenated. This reaction sequence has the advantage that derivatives are obtained in which R3 and R4 are produced exclusively as cis substituents. The compounds of formula I-cis can be converted to the corresponding compounds of formula I-trans by treatment with a base or an acid.

The pyrrolidin-2-ones of the formula I can be hydrolyzed with a strong acid or base to the corresponding 4-amino-butyric acid derivatives of the formula III, which is associated with partial isomerization of the R3 sub-substituent, so that a diastereoisomeric mixture is obtained which can be isolated as salts (for example HCl or sodium or magnesium etc.) or as free amino acids. The hydrolysis with Rl = alkyl takes place incompletely because of the formation of an equilibrium between the compounds of the formula I and III, which can be separated by extraction.

Another advantage of the present invention is that the reduction of the new pyrrolidin-2-ones of formula I e.g. with B2H6 or LÌAIH4 leads to the formation of new pyrrolidines of the formula II-cis (R3 and R4 cis) or of the formula II-trans (R3 and R4-trans) depending on the starting material. The hydrogenation of the C - C double bond in the compound the formula V is for example easily with hydrogen and about 5 to 15% of an about 10% palladium-on-carbon catalyst. Asymmetric hydrogenation is e.g. obtained by chiral rhodium catalysts (e.g. as described in J. Am. Chem. Soc., 19.77.99, 5946-52). Filtration and evaporation of the solvent, preferably methanol, directly gives the desired lactams of the formula I-cis in quantitative yield. When R1 = benzyl in formula V, the compound of formula I-cis with R1 = hydrogen can be obtained by hydrogenolysis, i.e. the N-benzyl group acts as a protecting group when R3 = hydrogen, alkyl or substituted alkyl.

The hydrolysis of the compounds of formula I under reflux in concentrated mineral acids (15 to 35%), e.g. HCl, followed by evaporation, leads directly to the formation of the corresponding 4-amino-butyric acid hydrochlorides of the formula III in the case of HCl. With sulfuric acid, the sulfates can be removed with barium hydroxide solution to obtain the free amino acids of formula III, which are converted into a desired carboxylic acid salt, e.g. the magnesium salt, or can be converted to an ammonium salt with a therapeutically acceptable acid. On the other hand, hydrolysis with a base leads to the corresponding carboxylic acid salts, e.g. the sodium or potassium salts.

The reduction of the carbonyl group in the lactams of formula I with e.g. Lithium aluminum hydride or borohydride leads to the formation of the corresponding pyrrolidines of the formula II, which can be converted into an ammonium salt with a therapeutically acceptable acid.

The following examples serve to further illustrate the present invention without, however, restricting it in any way.

example 1

3,4-diphenyl-3-pyrrolin-2-one (Va)

A solution of 12.6 g (50 millimoles) of 2-phenyl-acetamido-acetophenone in 200 ml of t-butanol slowly becomes a refluxed solution of potassium t-butoxide prepared from 6.5 g of potassium (166 millimoles) and 200 ml of t-butanol were added under nitrogen. After refluxing for 40 minutes, the solution is cooled to 40 ° C. and acidified to pH 6 to 5 with 2N HCl (about 120 ml). The suspension formed is poured into 3 liters of ice water. The precipitate is collected and washed with water. After drying, 9.85 g (84.1%) Va with a melting point of 183 to 190 ° C are obtained. Extraction of the water with chloroform gave a further 1.3 g (11.1%) Va.

A sample recrystallized from benzene gave a melting point of 177 to 179 ° C.

The following compounds of formula V were prepared in an analogous manner:

3-phenyl-4- (4'-chlorophenyl) -3-pyrrolin-2-one (Vb), melting point 204 to 210 ° C.

3- (2 '-carboxyphenyl) -4-phenyl-3-pyrrolin-2-one (Vc), melting point 238 to 241 ° C.

6

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

3-phenyl-4- (4'-fluorophenyI) -3-pyrrolin-2-one (Vd), melting point 200 to 202 ° C.

3- (4'-fluorophenyl) -4-phenyl-3-pyrrolin-2-one (Ve), melting point 199 to 209 ° C.

3-phenyl-4- (4'-methylphenyl) -3-pyrrolin-2-one (VI), melting point 210 to 220 ° C.

3-phenyl-4- (4 '- trifluoromethylphenyl) -3-pyrrolin-2-one (Vg), melting point 195 to 198 ° C.

3- (2'-fluorophenyl) -4- (4'-trifluoromethylphenyl) -3-pyrrolin-2-one (Vh), melting point 165 to 166 ° C. l, 3,5-trimetyhl-4-phenyl-3-pyrrolin-2-one (Vi), melting point 79 to 81 ° C.

1-Benzyl-4- (4'-trifluoromethylphenyl) -3-pyrrolin-2-one (Vk), rubber.

1-benzyl-3-methyl-4- (4'-trifluoromethylphenyl) -3-pyrroline

2-one (VI), rubber.

1,5-dimethyl-3,4-diphenyl-3-pyrrolin-2-one (Vm), melting point 95-103 ° C.

1,5-Dimethyl-4-phenyl-3-pyrrolin-2-one (Vn), melting point 130 to 135 ° C.

1-Methyl-3-phenyl-4- (4'-methylphenyl) -3-pyrrolin-2-one (Vo), melting point 123 to 124 ° C.

3-phenyl-4- (4'-methoxyphenyl) -3-pyrrolin-2-one (Vp), melting point 179 to 181 ° C.

3-phenyl-4- (3 ', 4'-dimethoxyphenyl) -3-pyrrolin-2-one (Vg), melting point 202-204 ° C.

3- (4'-fluorophenyl) -4-4'-trifluoromethylphenyl) -3-pyrroline

2-one (Vu), melting point 212 to 213 ° C.

Example 2

Cis-3,4-diphenyl-pyrrolidin-2-one (Cis-Ia)

A solution of 9.00 g of 3,4-diphenyl-3-pyrrolin-2-one (Va) in 200 ml of methanol and 0.90 g of 10% palladium-on-carbon were introduced into a 500 ml hydrogenation flask and kept for 16 Hydrogenated for hours at room temperature. The catalyst was filtered off and the methanol evaporated in vacuo. Crystallization from benzene-petroleum ether / 1: 1 gave crystals of melting point 154 to 155 ° C.

The following examples were prepared in an analogous manner:

3-phenyl-4- (4'-fluorophenyl) pyrrolidin-2-one (Cis-Id), melting point 198 to 200 ° C.

3- (4 '-fluorophenyl) -4-phenyl-pyrrolidin-2-one (Cis-Ie), melting point 167 to 168 ° C.

3-phenyl-4- (4'-methylphenyl) pyrrolidin-2-one (Cis-If), melting point 190 to 191 ° C.

3-phenyl-4- (4'-trifluoromethylphenyl) pyrrolidin-2-one (Cis-Ig), melting point 149 to 151 ° C.

3- (2 '-fluorophenyl (-4- (4' -trifluoromethylphenyl) pyrrolidine

2-one (Cis-Ih), melting point 154 to 156 ° C. l, 3,5-trimethyl-4-phenyl-pyrrolidin-2-one (Cis II), rubber.

4- (4'-Trifluoromethylphenyl) pyrrolidin-2-one (Ik), melting point 121 to 122 ° C.

3-methyl-4- (4'-trifluoromethylphenyl) pyrrolidin-2-one (Cis II).

1,5-dimethyl-4-phenyl-pyrrolidin-2-one (In), rubber. 1-Methyl-3-phenyl-4- (4'-methylphenyl) pyrrolidin-2-one (Cis-Io), melting point 113 to 114 ° C.

3-phenyl-4- (4'-methoxyphenyl) pyrrolidin-2-one (Cis-Ip), melting point 156 to 159 ° C.

3-phenyl-4- (3 '-dimethoxyphenyl) pyrrolidin-2-one (Cis-Iq), melting point 144 to 146 ° C.

3- (4 '-fluorophenyl) -4- (4'-trifluoromethylphenyl) pyrrolidin-2-one (Cis-Iu), melting point 203 to 204 ° C.

These compounds can be processed into further derivatives in a known manner, e.g .:

650772

(a) 1,5-Dimethyl-4- (4'-nitrophenyl) pyrrolidin-2-one (Ir) 4.32 g of the compound In was gradually added to 30 ml of fuming nitric acid at -5 to 0 ° C. After 1 hour at -10 ° C the solution was poured into 300 ml of water. Extraction with ethyl acetate and washing with bicarbonate solution and water gave 4.89 g (91.6%) of the compound Ir after evaporation of the solvent. Crystallization from acetone ether / 1: 3 gave crystals of melting point 94 to 95 ° C.

(b) 1,5-Dimethyl-4- (4'-chlorophenyl) pyrrolidin-2-one (It) A solution of 4.89 g (20.9 millimoles) of the compound Ir in 50 ml of methanol and 0.49 10% palladium-on-charcoal was charged into a 250 ml hydrogenation flask and hydrogenated at room temperature for 30 hours. The catalyst was filtered off and the methanol was distilled off in vacuo. The residue, l, 5-dimethyl-4- (4'-aminophenyl) pyrrolidin-2-one (Is), isolated in 100% yield, was dissolved in 12 ml of 18% hydrochloric acid in a 250 ml beaker and added dropwise treated with 5.23 ml of 4N sodium nitrite solution at 0 to 5 ° C. After 5 minutes at 0 ° C, the excess nitrite was destroyed with urea. After 10 minutes at 0 to 5 ° C, the diazonium solution was added dropwise to a freshly prepared solution of CuCl (20.9 millimoles) in 8 ml of 37% hydrochloric acid at 0 ° C. A brown precipitate formed immediately, which was heated to 60 ° C. for 1 hour. Extraction with chloroform and washing with water gave 4.30 g of crude reaction product after evaporation. After filtering through 130 g of silica gel, 3.80 g (81%) of the compound It was obtained as a gum.

(c) 4-Amino-2-phenyl-3- (4'-trifluoromethylphenyl) butyric acid hydrochloride (IIIg-HCl)

9.15 g of the compound cis-Ig were suspended in 300 ml of 25% HCl solution in a 500 ml flask and refluxed for 13 hours. After dilution with 300 ml of water and evaporation to dryness in vacuo, a white crystalline residue was obtained which was suspended in ether overnight to remove any lactam. Filtration and washing with ether gave 9.65 g (89.4%) of compound IIIg-HCl, melting point 182 to 183 ° C.

Analysis calculated for Ci7Hi7ClF3NC> 2 - 0.5 h2o (368.8):

Ber. %: C 55.37; H 4.85; N 3.80.

Found%: C 55.84; H 4.96; N 3.79

The following acid hydrochlorides were obtained in an analogous manner:

4-Amino-2,3-diphenyl-butyric acid HCl (purple HCl), melting point 210 to 222 ° C.

4-Amino-3- (4'-fluorophenyl) -2-phenyl-butyric acid-HCl (IIId-HCl), melting point 190 to 195 ° C.

4-Amino-2- (4'-fluorophenyl) -3-phenyl-butyric acid-HCl (Ille-HC1), melting point 170 to 175 ° C. 4-Amino-3- (4'-methylphenyl) -2-phenyl-butyric acid HCl (IIIf-HCl), melting point 210 to 216 ° C.

4-Amino-2- (2'-fluorophenyl) -3- (4'-trifluoromethylphenyl) butyric acid HCl (IIIh-HCl), melting point 182 to 185 ° C. 4-Amino-2- (4'-fluorophenyl-3- (4-trifluoromethylphenyl) butyric acid-HCl (IIIu-HCl), melting point 200 to 203 ° C. 4-Amino-3- (4'-trifluoromethylphenyl) -butyric acid-HCl (Illk-HC1), melting point 175 to 177 ° C. 4-Amino-2-methyl-3- (4'-trifluoromethylphenyl) -butyric acid-HCl (III1-HC1).

7

s

10th

15

20th

25th

30th

35

40

45

50

55

60

65

650772

4-Methylamino-4-methyl-3-phenyl-butyric acid-HCl (Illn-HC1), melting point 165 to 175 ° C.

4-Amino-3- (4'-methoxyphenyl-2-phenyl-butyric acid HCl (IIIp-HCl), melting point 190-210 ° C.

4-Amino-3- (3 ', 4' -dimethoxyphenyl) -2-phenyl-butter-acid-HCl (IIIq-HCl), melting point 230 to 233 ° C.

(d) 3,4-diphenyl-pyrrolidine (IIa)

A solution of 1.185 g cis-3,4-diphenyl-pyrrolidin-2-one (Ia) in 30 ml tetrahydrofuran (THF) was slowly added to a suspension of 0.950 g lithium aluminum hydride (LAH) and the mixture was heated under reflux for 7 hours . After cooling, 5 ml of ethyl acetate was added to destroy the excess of LAH and 7 ml of water was added to form the hydroxides. The suspension was filtered and washed with THF. The THF was removed in vacuo and the residue taken up in chloroform and extracted twice with 50 ml of 2N sulfuric acid. The water phase was treated with 2N NaOH solution until it became alkaline and extracted with chloroform. Crystallization of the residue from methylene chloride gave crystals of melting point 169 to 172 ° C. 0.05 ml of 37% HCl solution was then added to a solution of 0.100 g of compound IIa dissolved in 3 ml of methanol. Evaporation and suspension in ether gave 0.111 g of the compound Ila-HCl, melting point 74 to 84 ° C.

Example 3

A. N - [(4 '-trifluoromethylbenzoyl) methyll-2-2-bromace-tamide (Xllk)

A solution of 51.16 g (0.609 mol) of sodium bicarbonate in 550 ml of water was added under nitrogen at 0 to 10 ° C. to a two-phase solution of 48.5 g (0.203 mol) of 2-amino-4 '-trifluoromethylacetophenone hydrochloride (Xlk) added in 250 ml ether. A second solution of 18.41 ml (0.223 mol) of bromoacetyl chloride in 200 ml of dry ether was added to the above suspension at 0 to 5 ° C over 15 minutes with stirring. The initially thick suspension became thinner. After stirring for 2 hours, ethyl acetate was added until a clear two-phase solution was obtained. The water was separated and diethyl acetate-ether solution washed with water until it was neutral. Evaporation in vacuo gave 62.3 g (95%) of compound Xllk. A recrystallized sample gave a melting point of 201 to 211 ° C.

B. N - [(4'-Trifluoromethylbenzoyl) methyl] -2- (triphenylphosphonium bromide) acetamide (XIIIk)

70.5 g (0.269 mol) of triphenylphosphine were added to a suspension of 62.36 g (0.192 mol) of the compound Xllk in

600 ml of benzene added. After 4 days of stirring at room temperature, the solid was collected and suspended in 250 ml of acetone for 3 hours. Filtration gave 77.66 g (69%) of compound XHIk, melting point 250 to 251 ° C.

C. 4- (4'-Trifluoromethylphenyl) -3-pyrrolin-2-one (Vk)

72.5 ml of 2N NaOH solution were slowly added under a nitrogen atmosphere to a solution of 77.6 g (0.132 mol) of the compound XHIk in 780 ml of methanol in order to keep the temperature below 40 ° C. After stirring for 1 hour, 15 ml IN HCl solution was added to reach a pH of about 6.5. The methanol was partially evaporated in vacuo and completely removed after adding 200 ml of water. The precipitate was collected and washed with water. After drying, the residue, which weighed 67.25 g, was suspended in 200 ml of methylene chloride for 2 hours. Filtration gave 27.3 g (91%) of compound Vk with a melting point of 208 to 220 ° C. (dec.).

D. 4- (4-trifluoromethylphenyl) pyrrolidin-2-one (lk)

A solution of 27.2 g (0.12 mol) of compound Vk in

500 ml of methanol (partially suspended) was hydrogenated for 10 hours with 4.1 g of 10% Pd-on-carbon as a catalyst. Filtration and evaporation in vacuo gave 27.5 g (100%) of the compound Ik. A sample recrystallized from acetone ether / 1: 2 had a melting point of 121 to 122 ° C.

Analysis (C 11H10F3NO):

Ber. %: C 57.54; H 4.40; N 6.11 Found%: C 57.65; H 4.38; N 6.35.

This connection can e.g. be converted into the 4-amino-3- (4 '-trifluoromethylphenyl) butyric acid HCl (IIIk-HCl):

11.45 g (50 millimoles) of the compound Ik were heated under reflux in 100 ml of 25% HCl solution for 15 hours. After dilution with water and extraction with ether, the water phase was evaporated in vacuo. The residue was suspended in a little ether and collected. 13.45 g (95%) of the compound IIIk-HCl with a melting point of 175 to 177 ° C. were obtained.

Analysis (C11H13CIF3NO2):

Calc.%: C 46.57; H 4.62; N 5.94.%: C 46.44; H 4.67; N 5.06.

8th

s

10th

15

20th

25th

30th

35

40

45

50

B

Claims (4)

650772 2. The method according to claim 1, characterized in that the hydrogenation is carried out using a catalyst to form the 3,4-cis isomer of pyrrolidin-2-one. 2nd PATENT CLAIMS 1. Process for the preparation of a pyrrolidin-2-one of formula I: [IV] in which R1 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkanoyl, aroyl or one of the heteroaromatic radicals pyridyl, furyl, thienyl, N-alkyl-, N-arylpyrrolyl or their benzo derivatives, R3 is hydrogen, alkyl, substituted alkyl, aryl or substituted aryl, or one of those for R! defined heteroaromatic residues, R4 aryl, substituted aryl, one of the heteroaromatic radicals defined for R1, alkyl or substituted alkyl, R5 hydrogen, alkyl, substituted alkyl, aryl or substituted aryl or one of the for R! defined heteroaromatic residues, and R5 'represents hydrogen, alkyl or substituted alkyl, characterized in that a 3-pyrrolin-2-one of the formula V: in which R1, R3, R4, R5 and R5 'have the same meaning as above, is subjected to ring closure under basic conditions. 5. The method according to claim 4, characterized in that the ring closure takes place with potassium t-butoxide in t-butanol. 6. The method according to claim 5, characterized in that the reaction medium is acidified after the ring closure and diluted with water. 7. A process for the preparation of the starting materials of the formula V for the process according to claim 1, wherein the substituents R1, R3, R4, R5 and R5 'have the same meaning as in claim 1, characterized in that a phosphonium bromide of the formula XIII: [XIII] [V] in which R1, R3, R5 and R5 'has the same meaning as above, a ring closure in basic medium is under-4s. so pyrrolidin-2-ones of formula I: in which R1, R3, R4, R5 and R5 'have the same meaning as above, is subjected to the hydrogenation. 3rd 650772 or after isomerization 3. The method according to claim 2, characterized in that the catalyst is palladium-on-carbon, platinum or rhodium, optionally in the form of an optically active complex to form the optically active isomer of cis-pyrrolidin-2-one. 4. A process for the preparation of the starting materials of the formula V for the process according to claim 1, where the substituents R ", R3, R4, R5 and R5 'have the same meaning as in claim 1, but one of the substituents R5 and R5' is hydrogen, characterized in that a compound of formula IV: [I] and the corresponding pyrrolidines of the formula II: .4 in which R1 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkanoyl, aroyl or one of the heteroaromatic radicals pyridyl, furyl, thienyl, N-alkyl-, N-arylpyrrolyl or their benzo derivatives, R3 is hydrogen, alkyl, substituted alkyl, aryl or substituted aryl or one of the heteroaromatic radicals defined for R1, R4 aryl, substituted aryl, alkyl or substituted alkyl or one of the heteroaromatic radicals defined for R1, R5 hydrogen, alkyl, substituted alkyl, aryl or substituted aryl or one of the heteroaromatic radicals defined for R1, and R5 'represents hydrogen, alkyl or substituted alkyl include many known compounds which have interesting effects on the central nervous system (CNS) (Archivum Immunologiae et Therapiae Experimentalis, 1975, 23, 733-751). Many compounds of formula I have prostanglandin-like activity (DE-OS 2,527,989). The pyrrolidin-2-ones of the formula I have hitherto generally been obtained by ring closure of the corresponding 4-amino-butyric acid or its esters of the formula III: R5 R4 R3 I I I R'NH-C-CH-CH-CChR I. R5 '(III) (I-Trans) prepared by hydrogenation of 3-pyrrolin-2-ones of the formula V: (V) and 4-halo-butyric acid amides are obtained by reacting lac-tones with amines or by hydrolysis of 2-imino-pyrrolidines (British Patent 1,350,582 and US Patent 4,012,495). These processes for the preparation of compounds of formula I and II were limited in their efficiency, the nature of the substituents in the various positions and the difficulty in obtaining pure stereo and optically active isomers.