Method for preparing 2-amino-
Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group. Also disclosed is a compound, phenylmethyl N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]carbamate (a compound of Formula 4). Further disclosed is a method for preparing a compound of Formula 14 from a compound of Formula 15 and a compound of Formula 1 or 1A.
1. A method for preparing a salt having Formula 1A
wherein X is Cl
comprising
(A1) i) forming a reaction mixture by a) at a temperature between at least about 15° C. and no more than about 40° C., contacting in isopropyl acetate, a compound of Formula 8
with N,N′-carbonyldiimidazole, wherein the N,N′-carbonyldiimidazole reacts with the compound of Formula 8 to form a base derived from the N,N′-carbonyldiimidazole and an intermediate of Formula 9,
and then, after 1-2 hours,
b) adding to the reaction mixture a salt having Formula 3
which reacts with the intermediate of Formula 9 in the presence of the base derived from the N,N′-carbonyldiimidazole to form an intermediate of Formula 7
in the reaction mixture; and
ii) then washing the intermediate of Formula 7 in the reaction mixture by adding 1N HCl and removing water by azeotropic drying to produce a solution of intermediate of Formula 7 in isopropyl acetate; and
(B1) contacting the solution of intermediate of Formula 7 in isopropyl acetate, from step (A1) ii) with an acid of Formula 5
HX 5
to provide the compound of Formula 1A.
2. The method of claim 1 wherein in step (A1) the compound of Formula 8 and the salt having Formula 3 and the N,N′-carbonyldiimidazole are contacted in the presence of an additional base.
3. The method of claim 2 wherein the additional base is triethylamine.
4. The method of claim 1 wherein the hydrogen chloride is added as hydrogen chloride gas.
5. The method of claim 3 wherein the hydrogen chloride is added as hydrogen chloride gas.