2-phenylmethoxyaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-benzyloxynitrobenzene (9.92 g, 43.3 mmol) and NiCl2 (20.3 g, 157 mmol) in MeOH (350 mL) was added portionwise NaBH4 (8.09 g, 214 mmol) at 0° C. After disappearing of the starting material (monitored by TLC), the mixture was evaporated off. The black precipitate was dissolved in 1N HCl, then acidic solution was alkalified by the addition of 1N NaOH and extracted with EtOAc. The extracts were washed brine, dried over Na2SO4, and concentrated to dryness. Chromatography of the residue with CHCl3 as eluent gave 2-benzyloxy aniline (8.60 g, 100%) as a reddish oil. 1H-NMR (CDCl3) δ3.71 (broad s, 2H), 5.06 (s, 2H), 6.68-6.86 (m, 4H), 7.32-7.44 (m, 5H); FAB-MS m/z 200 (M++1). the mixture was evaporated off The black precipitate was dissolved in 1N HCl acidic solution was alkalified by the addition of 1N NaOH extracted with EtOAc The extracts were washed brine dried over Na2SO4 concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-benzyloxynitrobenzene (9.92 g, 43.3 mmol) and NiCl2 (20.3 g, 157 mmol) in MeOH (350 mL) was added portionwise NaBH4 (8.09 g, 214 mmol) at 0° C. After disappearing of the starting material (monitored by TLC), the mixture was evaporated off. The black precipitate was dissolved in 1 N HCl, then acidic solution was alkalified by the addition of 1 N NaOH and extracted with EtOAc. The extracts were washed brine, dried over Na2SO4, and concentrated to dryness. Chromatography of the residue with CHCl3 as eluent gave 2-benzyloxy aniline (8.60 g, 100%) as a reddish oil. 1H-NMR (CDCl3) δ 3.71 (broad s , 2H), 5.06 (s, 2H), 6.68–6.86 (m, 4H), 7.32–7.44 (m, 51); FAB-MS m/z 200 (M++1). the mixture was evaporated off The black precipitate was dissolved in 1 N HCl acidic solution was alkalified by the addition of 1 N NaOH extracted with EtOAc The extracts were washed brine dried over Na2SO4 concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using Procedure S-3 (Table 5) with 3-fluoroisonicotinic acid and 2-(benzyloxy)aniline the title compound 96 was obtained (4.01 g, 88%) as a white solid. MS (m/z): 323.2 (M+H). was obtained (4.01 g, 88%) as a white solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using Procedure S-3 (Table 5) with 3-fluoroisonicotinic acid and 2-(benzyloxy)aniline the title compound 96 was obtained (4.01 g, 88%) as a white solid. MS (m/z): 323.2 (M+H). was obtained (4.01 g, 88%) as a white solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-fluoroisonicotinic acid (2.20 g, 15.6 mmol), 2-(benzyloxy)aniline (2.84 g, 14.2 mmol) and BOP (6.94 g, 15.6 mmol) in DMF (20.0 mL) was added TEA (4.4 mL, 31.2 mmol). The reaction mixture was stirred at room temperature for 20 min and poured into water. The aqueous layer was extracted with ethyl acetate (2×). The combined organic extracts were washed with water and brine, dried over sodium sulfate and concentrated in vacuo to a quarter volume. The resulting solid was found to be the desired compound. The filtrate was concentrated in vacuo to dryness. The residue was triturated in 30% ethyl acetate in hexanes and the 2 solids were combined to afford compound 24 (4.45 g, 97%) as a white solid. LRMS (ESI): (calc) 322.11. (found) 323.2 (MH)+. The aqueous layer was extracted with ethyl acetate (2×) The combined organic extracts were washed with water and brine dried over sodium sulfate concentrated in vacuo to a quarter volume The filtrate was concentrated in vacuo to dryness The residue was triturated in 30% ethyl acetate in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-fluoroisonicotinic acid (2.20 g, 15.6 mmol), 2-(benzyloxy)aniline (2.84 g, 14.2 mmol) and BOP (6.94 g, 15.6 mmol) in DMF (20.0 mL) was added TEA (4.4 mL, 31.2 mmol). The reaction mixture was stirred at room temperature for 20 min and poured into water. The aqueous layer was extracted with ethyl acetate (2×). The combined organic extracts were washed with water and brine, dried over sodium sulfate and concentrated in vacuo to a quarter volume. The resulting solid was found to be the desired compound. The filtrate was concentrated in vacuo to dryness. The residue was triturated in 30% ethyl acetate in hexanes and the 2 solids were combined to afford compound 24 (4.45 g, 97%) as a white solid. LRMS (ESI): (calc) 322.11. (found) 323.2 (MH)+. The aqueous layer was extracted with ethyl acetate (2×) The combined organic extracts were washed with water and brine dried over sodium sulfate concentrated in vacuo to a quarter volume The filtrate was concentrated in vacuo to dryness The residue was triturated in 30% ethyl acetate in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Benzyloxyaniline (S1) (16.4 g), 4-dimethylamino-pyridine (11.0 g), and N-tertiarybutoxycarbonylglycine (14.4 g) were dissolved in dichloromethane. To the resulting solution, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (16.3 g) was added and stirred for 12 hours at room temperature. The reaction mixture was washed -successively with 1N HCl, saturated aqueous sodium hydrogencarbonate solution and brine, then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, obtaining 11.5 g of the compound S2 as white powder. The reaction mixture was washed -successively with 1N HCl, saturated aqueous sodium hydrogencarbonate solution and brine dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-benzyloxynitrobenzene (9.92 g, 43.3 mmol) and NiCl2 (20.3 g, 157 mmol) in MeOH (350 mL) was added portionwise NaBH4 (8.09 g, 214 mmol) at 0° C. After disappearing of the starting material (monitored by TLC), the mixture was evaporated off. The black precipitate was dissolved in 1N HCl, then acidic solution was alkalified by the addition of 1N NaOH and extracted with EtOAc. The extracts were washed brine, dried over Na2SO4, and concentrated to dryness. Chromatography of the residue with CHCl3 as eluent gave 2-benzyloxy aniline (8.60 g, 100%) as a reddish oil. 1H-NMR (CDCl3) δ3.71 (broad s, 2H), 5.06 (s, 2H), 6.68-6.86 (m, 4H), 7.32-7.44 (m, 5H); FAB-MS m/z 200 (M++1). the mixture was evaporated off The black precipitate was dissolved in 1N HCl acidic solution was alkalified by the addition of 1N NaOH extracted with EtOAc The extracts were washed brine dried over Na2SO4 concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-benzyloxynitrobenzene (9.92 g, 43.3 mmol) and NiCl2 (20.3 g, 157 mmol) in MeOH (350 mL) was added portionwise NaBH4 (8.09 g, 214 mmol) at 0° C. After disappearing of the starting material (monitored by TLC), the mixture was evaporated off. The black precipitate was dissolved in 1 N HCl, then acidic solution was alkalified by the addition of 1 N NaOH and extracted with EtOAc. The extracts were washed brine, dried over Na2SO4, and concentrated to dryness. Chromatography of the residue with CHCl3 as eluent gave 2-benzyloxy aniline (8.60 g, 100%) as a reddish oil. 1H-NMR (CDCl3) δ 3.71 (broad s , 2H), 5.06 (s, 2H), 6.68–6.86 (m, 4H), 7.32–7.44 (m, 51); FAB-MS m/z 200 (M++1). the mixture was evaporated off The black precipitate was dissolved in 1 N HCl acidic solution was alkalified by the addition of 1 N NaOH extracted with EtOAc The extracts were washed brine dried over Na2SO4 concentrated to dryness

Conditions: temp:0.00; pressure:0.00; stir: