* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Into a 1L 3-necked round-bottom flask was placed 4-methyl-5-nitro-2- (trifluoromethyl)pyridine (60 g, 291.26 mmol, 1 equiv), Fe (48.9 g, 873.79 mmol, 3 equiv), NH4CI (77.2 g, 1456.31 mmol, 5 equiv), and H2O (500 mL). The resulting mixture was stirred for 2 at 80 C. The resulting solution was extracted with ethyl acetate. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1/10) to give (27 g, 60.76%) of the title compound as a white solid. LC-MS: (ES, m/z): [M+H]+ 177.
60.76%
With iron; ammonium chloride; In water; at 80.0℃; for 2.0h;
Into a 1L 3-necked round-bottom flask was placed 4-methyl-5-nitro-2- (trifluoromethyl)pyridine (60 g, 291.26 mmol, 1 equiv), Fe (48.9 g, 873.79 mmol, 3 equiv), NH4CI (77.2 g, 1456.31 mmol, 5 equiv), and H20 (500 mL). The resulting mixture was stirred for 2h at 80 C. The resulting solution was extracted with ethyl acetate. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1/10) to give (27 g, 60.76%) of the title compound as a white solid. LC-MS: (ES, m/z): [M+H]+ 177.
With hydrogen;platinum(IV) oxide; In ethanol; for 5.5h;
A suspension of platinum oxide (36.9 mg) in a solution of 4-methyl-5-nitro-2-(trifIuoromethyl)pyridine (369.4 mg, 0.162 mmol) in EtOH (12.7 mL) was stirred under a balloon of H2 for 5 Vz h. The reaction mixture was filtered through a plug of Celite and the filtrate was concentrated in vacuo to afford 4- methyl-6-(trifluoromethyl)pyridin-3-amine. LCMS calc. = 177.1; found = 177.1 (M+l)+. 1H NMR (600 MHz, CDCl3): delta 8.04 (s, 1 H); 7.27 (s, 1 H); 4.28 (s, 2 H); 2.15 (s, 3 H).
With iodine; isopentyl nitrite; In chloroform; at 20.0℃; for 2.08333h;Heating / reflux;
Isoamyl nitrite (96%, 59 muL, 49.9 mg, 0.426 mmol) was added to a solution of 4-methyl-6- (trifluoromethyl)rhoyridin-3-amine (50.0 mg, 0.284 mmol) and iodine (79.2 mg, 0.312 mmol) in CHCl3 (1 mL) at room temperature under N2. The solution was stirred for 5 min then heated at reflux for 2 h. The reaction mixture was diluted with CHCI3, washed with saturated Na2SO3, dried (MgSO,*) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12 x 160 mm, 1-5% EtOAc in hexanes gradient) to afford 5-iodo-4-methyl-2-(trifluoromethyl)pyridine. R/ = 0.77 (10% EtOAc/hexanes). LCMS calc. = 288.0; found = 288.0 (M+l)+. 1H NMR (600 MHz, CDCl3): delta 8.96 (s, 1 H); 7.54 (s, 1 H); 2.50 (s, 3 H).
A solution of 4-methyl-6-(trifluoromethyl)pyridin-3-amine [944317-54-8] (1.00 g, 5.68 mmol) in acetic acid (75 mL) was treated with a solution of sodium nitrite (392 mg, 5.68 mmol) in water (1 mL). The reaction mixture was stirred at RT for 15 min and then was allowed to stand at ambient temperature for 48 h. Acetic acid was evaporated under reduced pressure and the residual aqueous solution was partitioned between EtOAc and sat. aq. NaHC03. The organic solution was washed with water and brine, then dried (Phase separator) and concentrated under vacuum. MS (LC-MS): 188 [M+H]+, tR (HPLC conditions k): 2.49 min.
(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[5-(4-fluoro-5-isopropyl-2-methoxyphenyl)-2-(trifluoromethyl)pyridin-4-yI]methyl}-4-methyl-1,3-oxazolidin-2-one[ No CAS ]
2-bromo-4-methyl-6-(trifluoromethyl)pyridin-3-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
96.45%
With N-Bromosuccinimide; In dichloromethane; for 2.0h;Inert atmosphere;
To a stirred solution <strong>[944317-54-8]4-methyl-6-(trifluoromethyl)pyridin-3-amine</strong> (27 g, 153.41 mmol, 1 equiv) in DCM (270 mL) was added NBS (27.1 g, 153.41 mmol, lequiv) in portions at 0 C under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 0 C under nitrogen atmosphere. The reaction mixture was quenched with water at room temperature and the resulting mixture was extracted with CH2CI2. The combined organic layers were dried over anhydrous Na2S04. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with PE/EtOAc (30/1) as eluent to afford (36.4 g, 96.45%) of the title compound as a red solid. LC-MS: (ES, m/z) [M+H]+ 255.
96.45%
With N-Bromosuccinimide; In dichloromethane; for 2.0h;Inert atmosphere;
To a stirred solution <strong>[944317-54-8]4-methyl-6-(trifluoromethyl)pyridin-3-amine</strong> (27 g, 153.41 mmol, 1 equiv) in DCM (270 mL) was added NBS (27.1 g, 153.41 mmol, lequiv) in portions at 0 C under nitrogen atmosphere. The resulting mixture was stirred for 2 h at 0 C under nitrogen atmosphere. The reaction mixture was quenched with water at room temperature and the resulting mixture was extracted with CH2CI2. The combined organic layers were dried over anhydrous Na2S04. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with PE/EtOAc (30/1) as eluent to afford (36.4 g, 96.45%) of the title compound as a red solid. LC-MS: (ES, m/z): [M+H]+255.
86%
With N-Bromosuccinimide; In dichloromethane; at 20.0℃; for 4.0h;
Over a solution of <strong>[944317-54-8]4-methyl-6-(trifluoromethyl)pyridin-3-amine</strong> (2 g, 11.35 mmol, 1 equiv) in dichloromethane (20 mL), NBS (2.0 g, 11.24 mmol, 0.990 equiv) was added. The resulting solution was stirred for 4 hr at room temperature and volatiles evaporated under vacuum. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1 :5) as eluent to afford the desired final product as a white solid in 86% yield.
86%
With N-Bromosuccinimide; In dichloromethane; at 20.0℃; for 4.0h;
Over a solution of <strong>[944317-54-8]4-methyl-6-(trifluoromethyl)pyridin-3-amine</strong> (2 g, 11.35 mmol, 1 equiv) in dichloromethane (20 mL), NBS (2.0 g, 11.24 mmol, 0.990 equiv) was added. The resulting solution was stirred for 4 hr at room temperature and volatiles evaporated under vacuum. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1 :5) as eluent to afford the desired final product as a white solid in 86% yield.
61%
With N-Bromosuccinimide; In water; dimethyl sulfoxide; at 20.0℃; for 48.0h;
N-Bromosuccinimide (594 mg, 3.34 mmol) was added to a stirred solution of 4-methyl- 6-(trifluoromethyl)pyridine-3-amine [944317-54-8] (235 mg, 1.33 mmol) in DMSO (5.6 mL) and water (310 pL). The reaction mixture was stirred at room temperature for 48 h and quenched with water. The aqueous phase was extracted with EtOAc (twice).The combined organic layers were dried (MgS04), filtered and concentrated in vacuo. The crude mixture was purified by flash column chromatography (silica,heptane/EtOAc, gradient from 100:0 to 85:15) to afford 1-163 (209 mg, 61%).