2-AMINO-4-CHLORO-BENZENEMETHANOL

General procedure: Iron powder (5.5 eq.) and NH4Cl (0.7 eq.) were suspended in EtOH : H2O 10 : 1 (0.05 M) and refluxedwith nitrophenyl derivative 12 (1 eq.) for 2 h. After completion (monitored by TLC analysis), thereaction mixture was filtrated on Celite® and rinsed with CH2Cl2. The solvent was evaporated underreduced pressure and CH2Cl2 was added. The mixture was washed with a saturated solution ofNaHCO3. The aqueous phase was extracted four times with CH2Cl2 and the combined organic phaseswere washed with brine, dried over magnesium sulfate and filtrated. Evaporation of the solvent underreduced pressure gave the desired product 11, which was used in the next step without furtherpurification.A suspension of (4-chloro-2-nitrophenyl)methanol (1 g, 5.33 mmol, ALDRICH) and platinum(IV) oxide (100 mg, 0.44 mmol) in ethanol (100 mL) was hydrogenated under 1300 mbar at room temperature for 1 hour. The resulting suspension was filtered, washed with ethanol and the filtrate concentrated to dryness to afford the crude (2-amino-4- chlorophenyl) methanol as a pale orange solid. The crude product was purified by flash 4-chloro-2-nitrophenyl)methanol (40.0 g, 0.21 mol) was dissolved in ethanol (700 mL) and hydrogenated under hydrogen gas (20 psi) in the presence of 5percent platinum on sulfided carbon (Pt-C/S, 5.00g). After 2 hours the catalyst was removed by filtration through CeliteGeneral procedure: To a solution of 6-chloroanthranilic acid (1.5 g, 8.74 mmol) in THF (5 mL) was added dropwise 1.08 M borane–tetrahydrofuran complex in THF (24.3 mL, 26.2 mmol) at 0 °C under an Ar atmosphere for 10 min. After 1.5 h with stirring at 30 °C, the solution was cooled at 0 °C, added aqueous THF (THF/HTo a mixture of L1AIH4 (4.4 g, 116.6 mmol) in dry THF (116 mL) at 0°C under N2 was added dropwise a solution of 2-amino-4-chlorobenzoic acid (10 g, 58.3 mmol) in dry THF (80 mL). The mixture was stirred at r.t. for 2 hr, then quenched, in sequence, by addition of H2O (4 mL), aq. NaOH (15 wt, 8 mL), and H2O (12 mL). The resulting mixture was filtered, and the filtrate was extracted with EtOAc. The combined organic layers were dried over anhydrous Na2SC>4 and concentrated under reduced pressure. The residue was re -crystallized from EtOAc/PE to give (2-amino-4-chlorophenyl)methanol (7.8 g, 85.4percent yield). LC-MS: m/z 158(M+H)+.In a 500 niL round bottom flask, the stirred solution of 2-amino-4-chlorobenzoic acid (42.8 g, 250.29 mmol, Aldrich) was dissolved anhydrous THF (200 mL) and the solution was cooled in an ice-bath. Lithium aluminum hydride (11.76 g, 312.86 mmol) was added portionwise to the above solution at the ice-bath temperature under nitrogen atmosphere. The resulting mixture was stirred at rt for 8 h. On completion of reaction the reaction mixture was cooled to ice-bath temperature and quenched by sequential addition of cold water (12 mL), 15percent NaOH (12 mL) and water (36 mL). The resulting slurry was stirred at rt for 30 min and filtered through a CELITE™ pad. The solid residue was washed with ethyl acetate (1000 mL) and combined filtrate was concentrated under reduced pressure to give (2-amino 4-chlorophenyl)methanol as an off white solid. Yield: 32g (81.6 percent). LCMS (ESI, m/z): 181 (M+23)(2-Amino-4-chlorophenyl)methanol. Methyl 2-amino-4-chlorobenzoate (1.5 g, 8.08 mmol) in THF (15 mL) was dropwise added to the suspension of LAH (429 mg, 11.3 mmol) in THF (10 mL) under N(2-Amino-4-chlorophenyl)methanol; Methyl 2-amino-4-chlorobenzoate (1.5 g, 8.08 mmol) in THF (15 mL) was dropwise added to the suspension of LAH(429 mg, 11.3 mmol) in THF (10 mL) under N

Molecular Weight:157.60
XLogP3:1.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:157.0294416
Monoisotopic Mass:157.0294416
Topological Polar Surface Area:46.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes