NO137498B - INTERMEDIATE PRODUCTION FOR LOCAL ANESTHETIC ACTIVITY 2- (N-N-PROPYL-TERT.-AMYLAMINO) -2`, 6`-ACETOXYLIDIDE - Google Patents

Description

The present invention relates to an intermediate product for use in the production of local anesthetic active 2-(N-n-propyl-tert.-amylamino)-2<1>, 6',-acetoxylidide.

The present intermediate product is characterized by the fact that it has the formula:

As for this intermediate's applicability to

preparation of the above-mentioned local anesthetic active compound, as well as its therapeutic data and advantages over

for previously known funds, reference is made to Norwegian application no.

792/73.

The following examples illustrate the preparation

of the present intermediate product, as example 1 also contains

means the direct use of the intermediate product for the production of the final product in question.

Example 1

A. N- n- propyl- tert.- amylamine - A suspension of 1.0 g

10% palladium on charcoal in 100 ml of absolute alcohol was shaken

with hydrogen until hydrogen absorption stopped. To the catalyst mixture was added 30 g (0.3442 mol) of tert-amylamine followed by a solution of 18 g (0.3098 mol) of propionaldehyde in 50 ml of absolute alcohol. All of the above ingredients were cooled in an ice bath before being combined. After heating to

room temperature, the reaction mixture was shaken with hydrogen at an initial pressure of approx.| 4 kg/cm 2 for 10 hours, at which time the theoretical amount of hydrogen had been absorbed. The catalyst was separated by filtration, washed with ethanol, after which 40 ml of concentrated hydrochloric acid was added to the combined filtrate. The solution was brought to dryness by evaporation in vacuo. The dried product was dissolved in 250 ml of distilled water, after which 160 g of 50% sodium hydroxide was slowly added with cooling to liberate the amine. The mixture was extracted with ether (3x200 mL), and the combined ether extracts were dried over anhydrous sodium sulfate. The dried extract was distilled through a 300 ml<1>s column packed with "ID-glass" spirals, and a total of 26.7 g (66.7%) of N-n-propyl-tert.-amylamine, boiling- point 136.5-137.5°C. (atmospheric pressure), n22Q 1.4106.

Analysis, calculated for CgH^N: C 74.34 H 14.82 N 10.84. Found: C 74.76 H 15.16 N 10.96.

B. 2-( N- n- propyl- tert.- amylamino)- 2', 6'- acetoxylidide-

150 ml of benzene was added to 10 g (0.0346 mol) of 2-iodo-2',6'-acetoxylidide and 11.8 g (0.0865 mol). N-n-propyl-tert-amylamine. The reaction mixture was refluxed for 29 hours. After cooling, the reaction mixture was distilled off for benzene and unreacted amine in vacuo. The resulting semi-solid was treated with anhydrous ether. The undissolved materials were filtered off and discarded while the ester was evaporated in vacuo. A yellow waxy material was obtained which was recrystallized twice from ethanol/water and twice from acetone/water. This gave a yield of 49.4% of a white crystalline material, melting point 96.5-97.5°C.

Analysis, calculated for C18H30<N>2O: C 74.43, H 10.41,

N 9.65. Found: C 74.4, H 10.35, N 9.59. Ir (KBr disk, base) 3240 (m, amide NH band), 1665 (s, amide I), 1495 (s, amide II), 1385 and 1370 (w, methyl CH bending) 766 (s, 3 adjacent aro- matic H atoms out of plane) cm . A hydrochloride was prepared from the base. This was obtained as a stable monohydrate with a melting point of 181.2-182.8°C.

Analysis, calculated for C18H31C1N20. H20: H20, 5.22 Found: (Karl Fischer) H20, 5.21.

Example 2

N- n- propyl- tert.- amylamine.

A mixture of 2 moles of tertiary amylamine and 1 mole of 1-bromopropane was refluxed for 6 hours. The reaction mixture was cooled and kept at +4°C for 1 hour. After filtration, the filtrate was fractionated by column distillation, and the colorless clear fraction boiling between 136 and 138°C was collected.

Claims (1)

Intermediate product for use in the production of local anesthetic active 2-(N-n-propyl-tert.-amylamino)-2',6'-acetoxylidide, characterized in that it has the formula: