N-(2-AMINO-4-TRIFLUOROMETHYLPHENYL)PIPERIDINE

Concentrated hydrochloric acid (2.00 ml, 24.0 mmol) and anhydrous tin dichloride (2.50 g, 13.1 mmol) were sequentially added at 0°C to a methanol (10 ml) solution containing 1-[2-nitro-4-(trifluoromethyl)phenyl]piperidine (559 mg, 2.03 mmol), obtained as described in Referential Example 1-1A. The resulting mixture was warmed to room temperature and then stirred for 17.5 hours. A saturated aqueous solution of sodium bicarbonate was added to the mixture. The resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with brine, dried over NaConcentrated hydrochloric acid (12.2 ml, 146 mmol) and anhydrous tin dichloride (12.7 g, 67.2 mmol) were sequentially added at 0°C to a dichloromethane solution (10 ml) of 1-[2-nitro-4-(trifluoromethyl)phenyl]piperidine (6.13 g, 22.4 mmol), obtained as described in Referential Example 1-1B. The resulting mixture was stirred for seven hours. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate = 15/1). Thus, 2-(1-piperidinyl)-5-(trifluoromethyl)aniline (4.55 g, 83.0percent) was yielded as a pale yellow solid.[Reference example 1-2B] A 50 mLround bottom flask initially placed in an ice bath was charged with10.8 mL (129.6 mmol) of concentrated hydrocloric acid, 6.71 g(35.4 mmol) of tin(II) chloride, 20.0 mL of methanol, and 1.50 g(5.47 mmol) of 1-(2-nitro-4-(trifluoromethyl)phenyl)piperidine(2). The ice bath was removed and the resulting mixture wascontinuously stirred at room temperature for 42 h. After this time, sodium hydroxide solution was added to the mixture until pH wasapproximately equal to 10. Then, the mixture was transferred to aseparatory funnel and extracted with ethyl acetate (4 x 80.0 mL).The organic extracts were combined and the resulting mixture waswashed with brine, dried under sodium sulphate, filtered andconcentrated under reduced pressure. The residue was purified bysilica gel column chromatography eluted with hexane-ethyl acetate(11:1 v/v). The compound 8 was obtained as a white solid in 78percentyield (1.34 g, 5.49 mmol). TLC Rf = 0.48 (hexane-ethyl acetate 11:1 v/v). mp 50.0-50.5 °C.IR (ATR, cm-1) νmax: 3452, 3355, 2950, 2865, 2805, 1611, 1589, 1512, 1469, 1439, 1379, 1328, 1288, 1256, 1227, 1205, 1160, 1104, 1064, 936, 892, 860, 810, 745, 722, 663, 643. 1H NMR (300 MHz, CDCl3) δ:1.60-1.75 (m, 6H), 2.88 (brs, 4H), 4.11 (brs, 2H, NH2), 6.93-7.03 (m, 3H). 13C NMR (75 MHz, CDCl3) δ: 24.4, 26.8, 52.4, 111.5 (q, J

Molecular Weight:244.26
XLogP3:3.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:244.11873297
Monoisotopic Mass:244.11873297
Topological Polar Surface Area:29.3
Heavy Atom Count:17
Complexity:249
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes