DE1269619B - Process for the preparation of 3-cyano-pyrrolidines - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

C07d

German class: 12p-2

Number: 1269 619

File number: P 12 69 619.4-44

Filing date: June 18, 1963

Opening day: June 6, 1968

The invention relates to a process for the preparation of 3-cyano-pyrrolidines of the formula I.

H ₃ C-

H ₂ C

C-CN

CH ₂

Process for the preparation of 3-cyanopyrrolidines

(D

in which X is a hydrogen atom or an alkyl, benzyl or phenyl group. The method of manufacture the new 3-cyano-pyrrolidines is characterized according to the invention in that a compound of formula II

H ₂ CH ₂ C

CH - shark CH ₂

(Π)

in which X has the meaning given above and Hal is a halogen atom, in the presence of Dimethyl sulfoxide is reacted with an alkali metal cyanide.

Chlorine, bromine or iodine pyrrolidine are preferably used as starting materials. These connections can by halogenation of the corresponding 1-substituted 3-pyrrolidinols means of the corresponding phosphorus trihalide.

Many of the compounds which can be prepared according to the process form characteristic complex compounds with copper and silver and can be used to precipitate them out of solution. The compounds also form valuable intermediates for the preparation of several Types of Pharmaceutically Active Compounds.

The implementation according to the method is explained in more detail below by means of exemplary embodiments.

Applicant:

AH Robins Company, Inc.,
Richmond, Va. (V. St. A.)

Representative:

Dr. G. W. Lotterhos

and Dr.-Ing. H. W. Lotterhos, patent attorneys,

6000 Frankfurt, Annastr. 19th

Named as inventor:

John Swidinsky, Newark, N. J .;

Bernard Beau Brown, Westfield, N. J. (V. St. A.)

Claimed priority:

V. St. v. America June 18, 1962 (202 971) - -

Example 1 1-methyl-3-cyano-pyrrolidine

and stirred for about 1 hour. When the mixture has cooled to room temperature, V21 chloroform is added to it. The chloroform mixture is poured into saturated saline solution, the chloroform layer is separated and the aqueous solution is extracted several times with small amounts of chloroform. The combined chloroform extracts are washed with saturated sodium chloride solution and the chloroform is distilled off. The residue, 1-methyl-3-cyano-pyrrolidine, is purified by vacuum distillation, bp. = 92 mm up to 93 ° C / 23 Hg, picrate mp. = 204-205 ⁰ C.

Example 2
1-ethyl-3-cyano-pyrrolidine

Using the procedure described in Example 1, 1-ethyl-1 mole of 1-methyl-3-bromopyrrolidine is obtained, 1-ethyl-potassium cyanide in ¹ ^ becomes 1.1 moles of 3-chloropyrrolidine as the starting product 1 Dimethyl sulfoxide given. 3-cyano-pyrrolidine, melting point = 102 to 104 ° C. / 23 mm Hg, the reaction mixture is heated to about 150 ° C. picrate, melting point = 140 to 14FC.

809 558/346

1 269 Ö19

Example 3
3-cyano-pyrrolidine

1.1 mol of sodium vanide is suspended in dimethyl sulfoxide at 90 ° C., and 1 mol of 3-chloro-pyrrolidine is slowly added to the solution. After the addition has been completed, the mixture is ^{heated to 150 to 160 °} C. for 20 minutes. After cooling, 2 mol of chloroform, which had previously been ^{cooled to 5 °} C., are added, and this mixture is poured into a saturated sodium chloride solution. The chloroform layer is separated from the aqueous layer, and the aqueous layer is extracted with pure chloroform. The chloroform extracts are combined with the decanted chloroform layer and the combined chloroform solution is washed with saturated saline. The chloroform is distilled off and the residue is subjected to vacuum distillation. Mp. Of the purified 3-cyanopyrrolidine 115 to 120 ° C / 50 mm Hg.

Example 4
1 -Benzyl-3-cyano-pyrrolidine

Following the procedure of Example 3, 1-benzyl-3-chloropyrrolidine is reacted with a 20% excess of sodium cyanide in dimethyl sulfoxide to give 1-benzyl-3-cyano-pyrrolidine, melting point = 120 ³ C / 0.4 mm Hg .

Claims (1)

Claim: Process for the preparation of 3-cyano-pyrrolidines of the general formula I. H ₂ CH ₂ C C-CN CH ₂ in which X is a hydrogen atom or an alkyl, benzyl or phenyl group, thereby characterized in that a compound of the general formula II H ₂ CH ₇ C - CH - shark CH, (II) in which X has the meaning given above and Hal is a halogen atom, in the presence of dimethyl sulfoxide is reacted with an alkali metal cyanide.