SU322050A1 - The method of obtaining-alkyl (aralkyl) -4-anilinopiperidines - Google Patents

Description

This invention relates to the field of the preparation of compounds which are intermediates for the synthesis of pharmaceutical preparations.

A method is known for producing N-alkl-4-anilinopiperidines by heating N-alkl-piperidone-4 with aniline in the presence of acidic catalysts, for example, P-toluene-sulphospot, followed by reduction of the lithium aluminum hydride and isolation of the desired product by a usual procedure.

There is also known a method for producing N-methyl-4-anilinopiperidinium iodide by heating N -1 "ethyl-4-phenoxypyridinium iodide with aniline.

A new method is proposed for the preparation of N-alkyl (aralkyl) -4-anilinopiperidines, which eliminates the need to use flammable lithium aluminum hydride and is less labor-intensive because it is based on more readily available raw materials.

The method consists in that 4-anilino-pyridine is reacted with alkyl halide (aralkyl), followed by reduction of the N-alkyl (aralkyl) -4-anilinopyridine sodium borohydride salt formed in the aqueous-alcoholic medium using C.-C .

alcohol or kx mixtures, and the selection of the target product in a known manner.

P and M - p 1. 17.1 g (0.1 mol) 1 - a1); glycine fndin and 15.6 g (11 mol of iv-methyl iodide boil in 10 O ml of absolute ethanol for 15 hours 500 ml of ethanol is distilled off under vacuum, 75 NOT of dry acetone is added and cooled to 0 ° C. The precipitate is separated, washed with 30 ml of cold acetone, 29.7 g of) N-M8til-4-aniline pyridin iodide yellowish crystals are obtained. mp. (with decomp.) 175- - 177 ° С.

The product is identical with the compound obtained by a known method.

Found,%: C 46.04; H 4.57; N9.12.

Claims (1)

Calculated,%: C 46,15; H 4.20; 8.97. yellowish crystals with so pl. 138-140 C (with decomp.). Found,%: C 57.22; H 6.10; N9.24, N, BH. Calculated C, 57.36; H 5.85; N9.55. Example 2. 1.71 g (0, O1 mol) 4 alkilinopyridine and 3.52 g (0.01 mol) of hexadeynyl iodide are mixed in a pro 6pjpKe with a ground plug, heated at 150 ° C to obtain a homogeneous alloy to hold at 90-1 OO ° C 2O hour After 6 hours, the alloy begins to crystallize. The resulting mass is triturated with acetone and ether. Obtain 4.7 g (90%) of yellowish crystals of N-hexadec 4-anilinopyridinium iodide. Found,%: C 63.79 :, And 8.14; S 5.60. C ,,, J bnx,%; C, 62.04; H 8.21; N 5.34 L and m 3. In a half-liter flask, 85.5 g (0.5 mol) of 4-anilinophene and 94 g (O, 5O5 mol) of j3 -phenylethyl bromide are charged. 5OO ml of acetone is added and refluxed for 12 hours. The precipitate of 4-aniline-opyridine gradually expands and a precipitate of crystalline N - (jJ phenylethyl) -4 aniline glygnidinium bromide begins to precipitate. The mixture is cooled to room temperature, the yellow crystals of the product are separated, washed with 100 ml of acetone and dried in air. Obtain 160 g (91%) of yellow crystals of methyl N - (|} -phenylethyl} -4-an. Orlynopyridini, mp. 188-190 C (with decomp.) Found:% C 65.41; H 3 , 84; N7.8 C, 9H, N, B. C 65.18 H 4.03; N8.00 Calculated, t Example 4. N-methyl-4-anilinopiperitsin. 21.2 g (0.1 mol) 4-anilino-N-methyridine iodisto1o is dissolved in 300 ml of ethanol, cooled to 15 ° C and, after cooling with cold water, the solution temperature is within 15-25 ° C, a solution of 5.7 g (0, 15 mol of sodium borohydride in 50 ml of 1% NaOH solution. Hold the solution for 2 hours at 15-25 ° C, remove the cooling and leave it for a day. evaporate to 50 ml, add potassium. potassium to saturate benzene to extract. Benzene is evaporated and the residue is crystallized from hexane and aqueous ethanol, Poluchak / g 17 g (84%) of colorless crystals — N Found,% 75.61j H 9.24; tsj 14.53. (2 C 75.78j H 9.55; Calculated, K | 14.74. 5. N-Hexadecyl-4-anis Example Linopiperidine. 5.24 g (0 , 01 mol) 4-anilino-N-hexadelated pyridinium iodide is dissolved in 50 ml of isopropanol and a solution of 0.76 g (0.02 mol) of sodium sulfonate in 10 ml of a 0.5% bicarbonate solution is added at 10-15 ° C. on three . Leave at room temperature for 20 hours. Isopropanol is distilled off under vacuum, 50 ml of water are added, it is cooled to 0 ° C and the product is separated. Crystallized from aqueous methanol. Obtain 3.26 g (80%) of colorless crystals of N-hexadecyl-4-anilinopiperidn, so pl. 44-45 S. T. pl. hydrochloride OO8209 0. Found,%: C 64.47; H 12.3.9; N 7.14. Calculated,%: C 64.27 H 12.10-. N 6.99. Example 6.N-benzyl-4-anilino-piperidine. 31.7 g (0.1 mol) of N-benzyl-4-anilinopyriam, dissolved in methyl bromide, are dissolved in 300 ml of methanol and treated at 5-15 C with a solution of 5.7 g (0.15 mol) of sodium borohydride in 50 ml 1 % solution of caustic soda. Leave for a day, evaporate to 100 ml, add ZOO ml of water, separate the precipitate, rinse thoroughly with cold water and crystallize from hexane. 18.6 g (86%) of colorless, N-benzyl-4-anilinopyridine crystals are obtained with a mp. 85-86 C. Found,%: C 81.44 H 8.19; N10.26. C, Calculated,%: C 81.16; H 8.32; N10.52. In the same way, N - (pphenylethyl) -4-anilinopiperidine is obtained from - (p ... -chienylethyl) -4 anilinopyridinium bromide in 88% yield. Colorless acetone crystals with m.p. 90-91 C. Found,%: C 81.30; H 8.71; ,eleven. C | . Calculated,%: C 81.37; H 8.63; N9.99. Invention Formula „322050 Ooh kil) followed by reduction of the acid in the aqueous-alcoholic medium and the salt thus converted with the N-alkyl of the target product known with (aralkyl) -4-anilinopyridinium borohydrideomem.