4-aminophenol;hydrochloride

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ0.93 (t, 3H), 1.38 (sextet, 2H), 1.70 (quintet, 2H), 2.79 (t, 2H), 4.27 (s, 1H), 4.35 (br. s, 1H), 6.62 (d, 2H), 6.75 (d, 2H), 7.18-7.26 (m, 3H), 7.41 (d, 1H), 7.54 (d, 1H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ0.93 (t, 3H), 1.38 (sextet, 2H), 1.70 (quintet, 2H), 2.79 (t, 2H), 4.27 (s, 1H), 4.35 (br. s, 1H), 6.62 (d, 2H), 6.75 (d, 2H), 7.18-7.26 (m, 3H), 7.41 (d, 1H), 7.54 (d, 1H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.110 g, 0.33 mmol), 4-hydroxyaniline hydrochloride (0.144 g, 0.99 mmol) and TEA (0.14 ml, 0.991 mmol) in DMF (0.5 ml) was heated at 140° C. for 25 mins in a microwave reactor. The mixture was purified by preparative HPLC (column Ace C8, 0.1M NH4OAc/MeCN, gradient) to give the title compound (0.074 g, 57%); 1H NMR 400 MHz (CDCl3) 7.26-7.20 (m, 2H), 7.18-7.14 (m, 3H), 7.08 (s, 1H), 6.62 (d, 2H), 6.48 (d, 2H), 3.78 (t, 2H), 1.91-1.84 (m, 2H), 1.53-1.45 (m, 2H), 1.02 (t, 3H); Mass Spectrum: M+H 373. The mixture was purified by preparative HPLC (column Ace C8, 0.1M NH4OAc/MeCN, gradient)

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ 0.93 (t, 3 H), 1.38 (sextet, 2 H), 1.70 (quintet, 2 H), 2.79 (t, 2 H), 4.27 (s, 1 H), 4.35 (br. s, 1 H), 6.62 (d, 2 H), 6.75 (d, 2 H), 7.18-7.26 (m, 3 H), 7.41 (d, 1 H), 7.54 (d, 1 H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ 0.93 (t, 3H), 1.38 (sextet, 2H), 1.70 (quintet, 2H), 2.79 (t, 2H), 4.27 (s, 1H), 4.35 (br. s, 1H), 6.62 (d, 2H), 6.75 (d, 2H), 7.18-7.26 (m, 3H), 7.41 (d, 1H), 7.54 (d, 1H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ0.93 (t, 3H), 1.38 (sextet, 2H), 1.70 (quintet, 2H), 2.79 (t, 2H), 4.27 (s, 1H), 4.35 (br. s, 1H), 6.62 (d, 2H), 6.75 (d, 2H), 7.18-7.26 (m, 3H), 7.41 (d, 1H), 7.54 (d, 1H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.110 g, 0.33 mmol), 4-hydroxyaniline hydrochloride (0.144 g, 0.99 mmol) and TEA (0.14 ml, 0.991 mmol) in DMF (0.5 ml) was heated at 140° C. for 25 mins in a microwave reactor. The mixture was purified by preparative HPLC (column Ace C8, 0.1M NH4OAc/MeCN, gradient) to give the title compound (0.074 g, 57%); 1H NMR 400 MHz (CDCl3) 7.26-7.20 (m, 2H), 7.18-7.14 (m, 3H), 7.08 (s, 1H), 6.62 (d, 2H), 6.48 (d, 2H), 3.78 (t, 2H), 1.91-1.84 (m, 2H), 1.53-1.45 (m, 2H), 1.02 (t, 3H); Mass Spectrum: M+H 373. The mixture was purified by preparative HPLC (column Ace C8, 0.1M NH4OAc/MeCN, gradient)