Trifluoroacetic acid → (4-Cyclohexyl-piperidin-4-ylmethyl)-thiazol-2-yl-amine

Reaction equation

FC(F)(F)C(O)=O.C(Cl)Cl.O.C(OC([N:19]1[CH2:24][CH2:23][C:22]([CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)([CH2:25][NH:26][C:27]2[S:28][CH:29]=[CH:30][N:31]=2)[CH2:21][CH2:20]1)=O)(C)(C)C.FC(F)(F)C(O)=O>>[CH:32]1([C:22]2([CH2:25][NH:26][C:27]3[S:28][CH:29]=[CH:30][N:31]=3)[CH2:21][CH2:20][NH:19][CH2:24][CH2:23]2)[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]1

Participants

Reactant 3

HCID 6422Trifluoroacetic acid

HCID 18672661TFA dichloromethane water

HCID 210237784-Cyclohexyl-4-(thiazol-2-ylaminomethyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 22185363(4-Cyclohexyl-piperidin-4-ylmethyl)-thiazol-2-yl-amineYield 96%

Procedure

A ready-to-use solution of trifluoroacetic acid:methylene chloride:water (1:1:0.1, 7 mL) is added to 4-cyclohexyl-4-(thiazol-2-ylaminomethyl)-piperidine-1-carboxylic acid tert-butyl ester, 12, (312 mg, 0.82 mmol), and the reaction mixture is stirred for 0.5–1.0 hour. The mixture is then concentrated under reduced pressure and partitioned between aqueous sodium bicarbonate and ethyl acetate. The organics are separated and the solvent removed under reduced pressure. The crude product is purified by preparative HPLC to afford 220 mg (96% yield) of the desired compound as the trifluoroacetic acid salt.