Process for preparing N-protected β-amino aldehyde compounds
View Patent ↗The invention provides processes for preparing N-protected β-amino aldehyde compounds which are useful as synthetic intermediates for preparing glycopeptide antibiotic derivatives. The processes include cleaving a carbon-carbon double bond to form the N-protected β-amino aldehyde compound.
1. A process for preparing a compound of formula I:
wherein R 1 is a 9-fluorenylmethoxycarbonyl group; and n is an integer from 7 to 11;
the process comprising cleaving the double bond of a compound of formula II:
wherein R 2 is hydrogen or C 1-12 hydrocarbyl;
wherein the step of cleaving the double bond comprises the steps of:
(a) reacting a compound of formula II with ozone to form an ozonide intermediate;
(b) reacting the ozonide intermediate from step (a) with a reducing agent to form a compound of formula I;
or the step of cleaving the double bond comprises the steps of:
(a) reacting a compound of formula II with a glycol-forming oxidizing agent to form a glycol intermediate;
(b) reacting the glycol intermediate from step (a) with a glycol-cleaving oxidizing agent to provide a compound of formula I.
2. The process according to claims 1 , wherein R 2 is hydrogen or C 1-12 alkyl.
3. The process according to claim 2 , wherein R 2 is hydrogen.
4. The process according to claim 1 , wherein n is an integer from 8 to 10.
5. The process according to claim 4 , wherein n is 9.
6. The process according to claim 1 , wherein R 2 is hydrogen; and n is 9.
7. The process according to claim 1 , wherein the step of cleaving the double bond comprises the steps of:
(a) reacting a compound of formula II with ozone to form an ozonide intermediate;
(b) reacting the ozonide intermediate from step (a) with a reducing agent to form a compound of formula I.
8. The process according to claim 7 , wherein the reducing agent is a trialkylamine.
9. The process according to claim 8 , wherein the reducing agent is triethylamine.
10. The process according to claim 1 , wherein the step of cleaving the double bond comprises the steps of:
(a) reacting a compound of formula II with a glycol-forming oxidizing agent to form a glycol intermediate:
(b) reacting the glycol intermediate from step (a) with a glycol-cleaving oxidizing agent to provide a compound of formula I.
11. The process according to claim 10 , wherein the oxidizing agent employed in step (a) and step (b) is the same and the oxidizing agent is sodium periodate and catalytic osmium tetroxide or ruthenium (IV) oxide.
12. A process for preparing a compound of formula I:
wherein R 1 is an amino-protecting group; and n is an integer from 7 to 11;
the process comprising the steps of:
(a) reacting a compound of formula III:
R 2 —CH═CH—CH 2 —NH 2 III
wherein R 2 is hydrogen or C 1-12 hydrocarbyl; with a compound of formula IV:
X—(CH 2 ) n —CH 3 IV
wherein X is a leaving group; to provide a compound of formula V:
(b) reacting the compound of formula V with an amino-protecting group reagent; to provide a compound of formula II:
(c) cleaving the double bond of the compound of formula wherein the step of cleaving the double bond comprises the steps of:
(a) reacting a compound of formula II with ozone to form ozonide intermediate;
(b) reacting the ozonide intermediate from step (a) with a reducing agent to form a compound of formula I;
or the step of cleaving the double bond comprises the steps of:
(a) reacting a compound of formula II with a glycol-forming oxidizing agent to form a glycol intermediate:
(b) reacting the glycol intermediate from step (a) with a glycol-cleaving oxidizing agent to provide a compound of formula I.
13. The process according to claim 12 , wherein R 1 is an amino-protecting group selected from the group consisting of tert-butoxycarbonyl; benzyloxycarbonyl; and 9-fluorenylmethoxycarbonyl.
14. The process according to claim 13 , wherein R 1 is a 9-fluorenylmethoxycarbonyl group.
15. The process according to claims 12 , wherein R 2 is hydrogen or C 1-12 alkyl.
16. The process according to claim 15 , wherein R 2 is hydrogen.
17. The process according to claim 12 , wherein n is an integer from 8 to 10.
18. The process according to claim 17 , wherein n is 9.
19. The process according to claim 12 , wherein X is chloro or bromo.
20. The process according to claim 19 , wherein X is bromo.
21. The process according to claim 1 , wherein R 1 is a 9-fluorenylmethoxycarbonyl group; R 2 is hydrogen; X is bromo; and n is 9.
22. A process for preparing a compound of formula Ia:
the process comprises the steps of:
(a) reacting allylamine with 1-bromodecane to provide a compound of formula Va:
(b) reacting the compound of formula Va with 9-fluorenylmethyl chloroformate; to provide a compound of formula IIa:
(c) reacting the compound of formula IIa with ozone to form an ozonide intermediate;
(d) reacting the ozonide intermediate from step (c) with a reducing agent to form a compound of formula Ia.
23. The process according to claim 22 , wherein the reducing agent is a trialkylamine.
24. The process according to claim 23 , wherein the trialkylamine is triethylamine.
25. The product prepared by the process of any of claims 7 , 10 , 12 , or 22 .