(S)-1-(3,5-bis(trifluoroMethyl)phenyl)-N-MethylethanaMine tosylate synthesis

Yield:97.7 % ee

Reaction Conditions:

in isopropyl alcohol at 20; for 3 h;Product distribution / selectivity;Heating / reflux;

Steps:

2

[Example 2] Purification of Optically Active (R)-1-(3,5-bis-trifluoromethylphenyl)ethylamine N-monomethyl (Salt Recrystallization Purification); Into 29.4 ml of i-propanol, 7.36 g (27.13 mmol, 1 eq) of a crude product of optically active (R)-1-(3,5-bis-trifluoromethylphenyl)ethylamine N-monomethyl (gas-chromatographic purity: 99.3%, enantiomeric excess: 89.7%ee) produced in the same manner as in Example 1 and 5.16 g (27.13 mmol, 1.00 eq) of p-toluenesulfonic acid monohydrate were added and dissolved under reflux condition followed by adding thereto 7.4 ml of methanol. The resulting mixture was let standing and cooled to room temperature. The mixture was then stirred for 3 hours so as to precipitate out a crystal. The precipitated crystal was filtered out and vacuum-dried, thereby obtaining 8.76 g of a recrystallization purification product of optically active (R)-1-(3,5-bis-trifluoromethylphenyl)ethylamine N-methyl salt of the following formula. [Show Image] The recovery was 72.8%. The gas-chromatographic purity and enantiomeric excess of the recrystallization purification product were 100% and 97.7%ee, respectively. The recovery was 76.4% on the basis of the optically active isomer (R-isomer). The recrystallization purification product of the salt was neutralized with 1N aqueous sodium hydroxide solution, extracted with toluene, condensed and vacuum-dried, thereby quantitatively obtaining a high-purity product (free base, oily matter) of optically active (R)-1-(3,5-bis-trifluoromethylphenyl)ethylamine N-monomethyl of the following formula.

References:

EP2036881,2009,A1 Location in patent:Page/Page column 17-18