(3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-1-benzofuran-3-yl)methanone

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

Procedure: At ambient temperature, to a stirred solution of commercial benzbromarone (0.243 g, 0.574 mmol) in 0.5M aq. NaHCO3:THF (8 mnL; 1:1) was added portionwise 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After the addition was complete the reaction was stirred for 18 h. To the reaction was added 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After 2 h, the reaction was quenched with 2N HCl (25 mL), extracted with EtOAc and concentrated. The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) and crystallized from EtOAc/hexane to give 0.14 g (39%) of the title compound as a white solid, mp 173° C.; 1H NMR (DMSO-d6) δ1.25 (t, 3H), 2.76 (q, 2H), 7.30 (dt, 1H), 7.36 (dt, 1H), 7.44-7.49 (m, 3H), 7.66 (d, 1H), 8.03 (d, 1H), 8.08 (s, 2H). IR (KBr) 3400, 2950, 1680, 1650, 1400 and 1180 cm−1. mass spectrum (−ESI), m/z 621/623/625 (M−H). Anal. Calcd. for C24H16Br2O8S: C, 46.18; H, 2.58; N, 0.00. Found: C, 46.41; H, 2.64; N, 0.00. while maintaining the pH at 8 After the addition while maintaining the pH at 8 After 2 h the reaction was quenched with 2N HCl (25 mL) extracted with EtOAc concentrated The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) crystallized from EtOAc/hexane

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

Procedure: At ambient temperature, to a stirred solution of commercial benzbromarone (0.243 g, 0.574 mmol) in 0.5M aq. NaHCO3:THF (8 mnL; 1:1) was added portionwise 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After the addition was complete the reaction was stirred for 18 h. To the reaction was added 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After 2 h, the reaction was quenched with 2N HCl (25 mL), extracted with EtOAc and concentrated. The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) and crystallized from EtOAc/hexane to give 0.14 g (39%) of the title compound as a white solid, mp 173° C.; 1H NMR (DMSO-d6) δ1.25 (t, 3H), 2.76 (q, 2H), 7.30 (dt, 1H), 7.36 (dt, 1H), 7.44-7.49 (m, 3H), 7.66 (d, 1H), 8.03 (d, 1H), 8.08 (s, 2H). IR (KBr) 3400, 2950, 1680, 1650, 1400 and 1180 cm−1. mass spectrum (−ESI), m/z 621/623/625 (M−H). Anal. Calcd. for C24H16Br2O8S: C, 46.18; H, 2.58; N, 0.00. Found: C, 46.41; H, 2.64; N, 0.00. while maintaining the pH at 8 After the addition while maintaining the pH at 8 After 2 h the reaction was quenched with 2N HCl (25 mL) extracted with EtOAc concentrated The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) crystallized from EtOAc/hexane

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

Procedure: At ambient temperature, to a stirred solution of commercial benzbromarone (0.243 g, 0.574 mmol) in 0.5M aq. NaHCO3 :THF (8 mL; 1:1) was added portionwise 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After the addition was complete the reaction was stirred for 18 h. To the reaction was added 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After 2 h, the reaction was quenched with 2N HCl (25 mL), extracted with EtOAc and concentrated. The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) and crystallized from EtOAc/hexane to give 0.14 g (39%) of the title compound as a white solid, mp 173° C.; 1H NMR (DMSO-d6) δ 1.25 (t, 3 H), 2.76 (q, 2 H), 7.30 (dt, 1 H), 7.36 (dt, 1 H), 7.44-7.49 (m, 3 H), 7.66 (d, 1 H), 8.03 (d, 1 H), 8.08 (s, 2 H). IR (KBr) 3400, 2950, 1680, 1650, 1400 and 1180 cm-1, mass spectrum (-ESI), m/z 621/623/625 (M-H). Anal. Calcd. for C24H16Br2O8S: C, 46.18; H, 2.58; N, 0.00. Found: C, 46.41; H, 2.64; N, 0.00. while maintaining the pH at 8 After the addition while maintaining the pH at 8 After 2 h the reaction was quenched with 2N HCl (25 mL) extracted with EtOAc concentrated The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) crystallized from EtOAc/hexane

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

Procedure: At ambient temperature, to a stirred solution of commercial benzbromarone (0.243 g, 0.574 mmol) in 0.5M aq. NaHCO3:THF (8 mL; 1:1) was added portionwise 4-chiorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After the addition was complete the reaction was stirred for 18 h. To the reaction was added 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After 2 h, the reaction was quenched with 2N HCl (25 mL), extracted with EtOAc and concentrated. The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H20 containing 0.1% TFA) and crystallized from EtOAc/hexane to give 0.14 g (39%) of the title compound as a white solid, mp 173° C.; 1H NMR (DMSO-d6) δ1.25 (t, 3 H), 2.76 (q, 2 H), 7.30 (dt, 1 H), 7.36 (dt, 1 H), 7.44-7.49 (m, 3 H), 7.66 (d, 1 H), 8.03 (d, 1 H), 8.08 (s, 2 H). IR (KBr) 3400, 2950, 1680, 1650, 1400 and 1180 cm−1. mass spectrum (−ESI), m/z 621/623/625 (M−H). Anal. Calcd. for C24H16Br2O8S: C, 46.18; H, 2.58; N, 0.00. Found: C, 46.41; H, 2.64; N, 0.00. while maintaining the pH at 8 After the addition while maintaining the pH at 8 After 2 h the reaction was quenched with 2N HCl (25 mL) extracted with EtOAc concentrated The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H20 containing 0.1% TFA) crystallized from EtOAc/hexane

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

Procedure: At ambient temperature, to a stirred solution of commercial benzbromarone (0.243 g, 0.574 mmol) in 0.5M aq. NaHCO3:THF (8 mL; 1:1) was added portionwise 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After the addition was complete the reaction was stirred for 18 h. To the reaction was added 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After 2 h, the reaction was quenched with 2N HCl (25 mL), extracted with EtOAc and concentrated. The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) and crystallized from EtOAc/hexane to give 0.14 g (39%) of the title compound as a white solid, mp 173° C.; 1H NMR (DMSO-d6) δ 1.25 (t, 3H), 2.76 (q, 2H), 7.30 (dt, 1H), 7.36 (dt, 1H), 7.44-7.49 (m, 3H), 7.66 (d, 1H), 8.03 (d, 1H), 8.08 (s, 2H). IR (KBr) 3400, 2950, 1680, 1650, 1400 and 1180 cm−1. mass spectrum (−ESI), m/z 621/623/625 (M−H). Anal. Calcd. for C24H16Br2O8S: C, 46.18; H, 2.58; N, 0.00. Found: C, 46.41; H, 2.64; N, 0.00. while maintaining the pH at 8 After the addition while maintaining the pH at 8 After 2 h the reaction was quenched with 2N HCl (25 mL) extracted with EtOAc concentrated The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) crystallized from EtOAc/hexane

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

Procedure: At ambient temperature, to a stirred solution of commercial benzbromarone (0.243 g, 0.574 mmol) in 0.5M aq. NaHCO3:THF (8 mnL; 1:1) was added portionwise 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After the addition was complete the reaction was stirred for 18 h. To the reaction was added 4-chlorosulphonyl-2-hydroxybenzoic acid (0.271 g, 1.15 mmol) while maintaining the pH at 8 with the simultaneous addition of 0.5M aq. NaHCO3. After 2 h, the reaction was quenched with 2N HCl (25 mL), extracted with EtOAc and concentrated. The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) and crystallized from EtOAc/hexane to give 0.14 g (39%) of the title compound as a white solid, mp 173° C.; 1H NMR (DMSO-d6) δ1.25 (t, 3H), 2.76 (q, 2H), 7.30 (dt, 1H), 7.36 (dt, 1H), 7.44-7.49 (m, 3H), 7.66 (d, 1H), 8.03 (d, 1H), 8.08 (s, 2H). IR (KBr) 3400, 2950, 1680, 1650, 1400 and 1180 cm−1. mass spectrum (−ESI), m/z 621/623/625 (M−H). Anal. Calcd. for C24H16Br2O8S: C, 46.18; H, 2.58; N, 0.00. Found: C, 46.41; H, 2.64; N, 0.00. while maintaining the pH at 8 After the addition while maintaining the pH at 8 After 2 h the reaction was quenched with 2N HCl (25 mL) extracted with EtOAc concentrated The crude product was purified by preparative HPLC (C18, eluting with 75% CH3CN/H2O containing 0.1% TFA) crystallized from EtOAc/hexane