Method for preparing 2-amino-N-(2,2,2-trifluoroethyl) acetamide
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 compound of Formula 1A
wherein X is Cl, Br, CF 3 CO 2 , CH 3 SO 3 , (SO 4 ) 1/2 or (PO 4 ) 1/3 , comprising
(A1) in a water immiscible solvent, contacting a compound of Formula 8
with a coupling reagent, wherein the coupling reagent is N,N′-carbonyldiimidazole and reacts with Formula 8 to form a base derived from the coupling reagent and an intermediate of Formula 9,
and then after 1-2 hours, adding a salt having Formula 3
to the intermediate of Formula 9 in the presence of the base derived from the coupling reagent, wherein the intermediate of Formula 9 and the salt having Formula 3 react to form an intermediate of Formula 7
and
(B1) contacting the intermediate of Formula 7 with an acid of Formula 5
HX 5
to provide the compound of Formula 1A.
2. The method of claim 1 step (B1) wherein the compounds of Formulae 7 and 5 are contacted in the presence of a water immiscible solvent.
3. The method of claim 2 wherein the acid of Formula 5 comprises hydrogen chloride.
4. The method of claim 1 wherein the water immiscible solvent comprises ethyl acetate or iso-propyl acetate.
5. The method of claim 2 wherein the water immiscible solvent comprises ethyl acetate or iso-propyl acetate.