(2-AMINO-6-CHLORO-PHENYL)-METHANOL

Dissolves 50.0 g (286 mmol) of 2-amino-6chlorophenyl acid in 300 ml of anhydrous THF (Tetrahydrofuran)(2-Amino-6-chlorobenzoic acid) mixture, cooling the solution to 0 ~ 10 °C, Add 450ml of 1.0M lithium aluminum hydride THF solution, The reaction mixture was allowed to warm to room temperature and then stirred at room temperature overnight.300 ml of 10percent NaOH aqueous solution was added to the reaction mixture, The organic phase was separated and washed with ethyl acetate and water. After drying with magnesium sulfate, The solvent was removed in vacuo to give 42 g (270 mmol, 95percent) of the product as a yellow solid.No further purification.General 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/H3.43 g (20.0 mmol) of 2-amino-6-chlorobenzoic acid was dissolved in anhydrous THF 30 mL), to which LiAlHTo prepare this compound, lithium aluminum hydride (3.3 g, 88 mmol) was added in three portions to a suspension of 2-amino-6-chlorobenzoic acid (5.0 g, 29 mmol) in THF (145 mL) at 0 °C. That reaction was allowed to warm to room temperature and was stirred for 2 hours. Then the reaction was quenched slowly with ethyl acetate/methanol while cooling in an ice bath. That quenched suspension was filtered, washed with ethyl acetate/methanol and filtered. The filtrate was concentrated under reduced pressure and the resultant material was purified by flash chromatography (4:1 hexanes:ethyl acetate) to afford 2.75 g (61percent) of 2-(amino-6-chlorophenyl)methanol.To a suspension of lithium aluminium hydride(1.1g, 29.1 mmol) in tetrahydrofuran (150 ml) was added 2-amino-6-chlorobenzoic acid (5g, 29.1 mmol) at 0C. The mixture was stirred at room temperature for 16h. Then, the reaction mixture was quenched with sodium sulfate decahydrate (3 gh) and brine ( 10 ml) and filtrated through a pad of celite. The organic layer was concentrated in vacuo and the residue was chromatographed on a column of silica gel eluting with ethylacetate/hexane (1:2) to give 2.4 g (52percent) of the title compound as a colorless oil.1H-NMR (CDCL3) d: 7.01 (1 H, dd, J=7.9, 8.1Hz), 6.76 (1 H, d, J= 7.9 Hz), 6.58 (1 H, D, J=8.1 Hz) 4.88(2H, S). Signals due to NH2 and OH were not observed.In a 500 mL two-necked round bottom flask, 1-1 (25.0 g, 143 mmol) was dissolved in 120 mL anhydrous THF. The solution was cooled in an ice water bath, and then 215 mL of a 1.0 M lithium aluminum hydride (LAH) THF solution was added dropwise. After all the LAH had been added, the reaction mixture was warmed to room temperature and stirred at room temperature overnight. 10 mL of water was added to the reaction mixture followed by 7 g of 15percent NaOH. An additional 20 g of water was added to the reaction mixture. The organic THF phase was decanted and ethyl acetate was added as a solid. It was added to 200 mL and stirred, and the ethyl acetate organic portion and the THF portion were combined and a Na 2 SO 4 desiccant was added. Filter and evaporate the mixture.Yield 20g of yellow solid, No further purification was carried out for the next reaction.