Method of preparation of (s)-n-tert-butyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
View Patent ↗A new method is described here for the synthesis of (S)-N-tert-butyl-1,2,3,4-tetrahydroiso-quinoline-3-carboxamide comprising the following steps: a) (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is reacted with formic acid to give the compound of formula: b) the compound thus obtained is reacted with tert-butylamine to give the compound of formula: c) the compound thus obtained is then treated with acids to give the desired compound. The method in question makes it possible to obtain (S)-N-tert-butyl-1,2,3,4-tetrahydroiso-quinoline-3-carboxamide with high yields and purity without using toxic and hazardous reagents.
1. A method of preparation of (S)-N-tert-butyl-1,2,3,4 tetrahydmisoquinoiine-3-carboxamide comprising the following steps:
a) (3S)-1,2,3,4-tetrahydroisoqulnoline-3-carboxyiic acid is reacted with formic acid to give the compound of formula:
b) the compound thus obtained is reacted with tert-butylamine to give the compound of formula:
the compound thus obtained is then treated with at least one second acid to give (S)-N-tert-butyl-1 ,2,3.4-tetrahydroisoquinoline-3-carboxamide.
2. A method according to claim 1 , wherein step (a) is carried out in toluene.
3. A method according to claim 1 , wherein step (a) is carried out in the presence of acetic anhydride.
4. A method according to claim 1 , wherein step (a) is carried out at a temperature of 30-70 C.
5. A method according to claim 1 , wherein step (b) is carried out in ethyl acetate.
6. A method according to claim 1 , wherein step (b) is carried out in the presence of triethylamine and/or ethyl chloroformate.
7. A method according to claim 1 , wherein step (b) is carried out at a temperature between −20 and +10° C.
8. A method according to claim 1 , wherein step (c) is carried out in dioxan and hydrochloric acid.
9. A method according to claim 1 , wherein step (c) is carried out at a temperature between 10 and 40° C.
10. A method according to claim 1 , wherein (S)-N-tert-butyl-1,2,3,4-tetra-hydroisoquinoline-3-carboxamide is hydrogenated to give N-tert-butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide.
11. A method according to claim 1 , wherein (3S)-1,2.3,4-tetrahydroiso-quinollne-3-carboxylic acid is obtained by reaction of 1-phenylalanane with formal-dehyde, preferably paraformaldehyde.
12. A method according to claim 4 , wherein step (a) is carried out at a temperature of about 50° C.
13. A method according to claim 7 , wherein step (b) is carried out at a temperature of about −2° C.
14. A method according to claim 9 , wherein step (c) is carried out at a temperature of about 25° C.