3-AMINO-5-TRIFLUOROMETHYL-BENZOIC ACID METHYL ESTER

To a mixture of methyl 3-nitro-5- (trifluoromethyl)benzoate (350 mg, 1.40 mmol) and tin(II) chloride dihydrate (1.58 g, 7.02 mmol) in methanol (20 mL) was added water (1 mL) and the resulting mixture was stirred at 70 °C for 2 h. After cooling to room temperature, the reaction mixture was concentrated and was quenched by the addition of saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate (3X). The combined organic portion was dried over magnesium sulfate, was filtered and was concentrated to give methyl 3-amino-5- (trifluoromethyl)benzoate (300 mg, 98percent yield) as a colorless solid. To a solution of methyl 3-nitro-5-(trifluoromethyl) benzoate (1.50 g, 6.02 mmol) in methanol (20 . mL) was added palladium carbon (50percent water-containing product, 15 mg) , and the mixture was stirred under a hydrogen atmosphere at room temperature for 3 hr. The reaction mixture was filtered through celite. The filtrate was concentrated under reduced pressure and dried to give the title compound(1.27 g, 96percent) as a white solid.Reference Example 28Methyl 3-amino-5-(trifluoromethyl)benzoate. Methyl 3-nitro-5-(trifluoromethyl)benzoate (9.0 g, 36.1 mmol) in methanol (30 mL) was flushed with nitrogen, and treated with palladium (10percent on charcoal, 0.90 g). The flask was flushed with hydrogen and allowed to stir under an atmosphere of hydrogen overnight. The reaction was flushed with nitrogen, filtered through celite, and concentrated. Flash chromatography on silica gel (30percent ethyl acetate/hexanes) afforded 6.8 g (86percent). A solution of 3-nitro-5-trifluoromethyl-benzoic acid methyl ester (8.6 mmol, 2.15 g) and tin chloride dihydrate (25.8 mmol, 5.82 in ethanol (40 ml) is allowed to warm to 60 (Reference Example 28) To a solution of 3-nitro-5-(trifluoromethyl)benzoic acid (1.0 g, 4.25 mmol) in methanol, a catalyst amount of p-toluenesulfonic acid was added, and the obtained solution was heated under reflux for 15 hours. The obtained reaction liquid was returned to room temperature and then concentrated to the half of the original volume. Palladium (10percent by weight) on carbon (containing 50percent water by weight, 0.062 g) was added to the reaction liquid, and the obtained solution was stirred for one hour under hydrogen atmosphere. The reaction liquid was filtered through Celite®, the filtrate was concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (eluent; hexane:ethyl acetate = 90:10 → 60:40) to obtain the title compound (0.85 g). MS(ESI) [M + H]

Molecular Weight:219.16
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:2
Exact Mass:219.05071298
Monoisotopic Mass:219.05071298
Topological Polar Surface Area:52.3
Heavy Atom Count:15
Complexity:242
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes