Improved Methodology for the Preparation of Chiral Amines

ethyl carbamate by acylation with ethyl chloroformate. Benzyl carbamate group on the
nitrogen at 4 position is hydrogenolyzed using ammonium formate over palladium forming
the primary amine. The chiral amine is resolved as debenzyl tartarate salt to afford (2R, 4S)
isomer. Bis-trifuoromethyl benzaldehyde and sodiumtriacetoxy borohydride are used for the
reductive amination of the pure isomeric amine which is then acylated with chloroformate
forming the final product.
F 3 C
F 3 C
5
1
HN
N
H
O
NH 2
O
CH 2 C 5 H 5
CHO
ClCO 2 C 2 H 5
CF 3
NH 2 1.
F 3 C
F 3 C CHO
N
2. CH 3 OCOCl
C 2 H 5
O O
7
2
N
N
N
H
F 3 C
O
N
N
N
N
H
CH 2 C 5 H 5
HN O
1. HCO - +
2 NH 4
F 3 C
Pd
N
2.resolve
C 2 H 5
O O
6
O
F 3 C
O
C 2 H 5
O
8
N
N
O
3
CF 3
CF 3
vinyl carbamate
Scheme 4.13.Synthesis of Torcetrapib:
4.1.14. Synthesis of Polyaminocholestanol derivatives:
Polyaminocholestanol derivatives are used as potent antibiotics for highly resistant bacterial
strains (superbugs). [9] The key step in their synthesis is reductive amination. Different
titanium sources were tested in different solvents. The highest des were obtained when
Ti(O i Pr) 4 was used with MeOH and NaBH as hydride source. Different amine and diamaines
were tested and the des were higher than 95% but the yields were poor to mediocre (6-77%).
93