2,3-dichloro-4-fluoroaniline

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H). To an oven-dried, N2-purged 100-mL, round-bottomed flask containing a magnetic stir bar The flask was sealed with a septum to warm to room temperature for 2 hours The mixture was transferred to a separatory funnel extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over magnesium sulfate filtered concentrated by rotary evaporator to give a brown semi-solid The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H). To an oven-dried, N2-purged 100-mL, round-bottomed flask containing a magnetic stir bar The flask was sealed with a septum to warm to room temperature for 2 hours The mixture was transferred to a separatory funnel extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over magnesium sulfate filtered concentrated by rotary evaporator to give a brown semi-solid The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H). To an oven-dried, N2-purged 100-mL, round-bottomed flask containing a magnetic stir bar The flask was sealed with a septum to warm to room temperature for 2 hours The mixture was transferred to a separatory funnel extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over magnesium sulfate filtered concentrated by rotary evaporator to give a brown semi-solid The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H). To an oven-dried, N2-purged 100-mL, round-bottomed flask containing a magnetic stir bar The flask was sealed with a septum to warm to room temperature for 2 hours The mixture was transferred to a separatory funnel extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over magnesium sulfate filtered concentrated by rotary evaporator to give a brown semi-solid The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H). To an oven-dried, N2-purged 100-mL, round-bottomed flask containing a magnetic stir bar The flask was sealed with a septum to warm to room temperature for 2 hours The mixture was transferred to a separatory funnel extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over magnesium sulfate filtered concentrated by rotary evaporator to give a brown semi-solid The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H). To an oven-dried, N2-purged 100-mL, round-bottomed flask containing a magnetic stir bar The flask was sealed with a septum to warm to room temperature for 2 hours The mixture was transferred to a separatory funnel extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over magnesium sulfate filtered concentrated by rotary evaporator to give a brown semi-solid The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H). To an oven-dried, N2-purged 100-mL, round-bottomed flask containing a magnetic stir bar The flask was sealed with a septum to warm to room temperature for 2 hours The mixture was transferred to a separatory funnel extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over magnesium sulfate filtered concentrated by rotary evaporator to give a brown semi-solid The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an oven-dried, N2-purged, 100-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 192B (3.08 g, 11.0 mmol) and dichloromethane (25 mL). The flask was sealed with a septum and cooled to 0° C. in an ice bath. Trifluoroacetic acid (18 mL) was added dropwise via syringe. The brown solution was stirred at 0° C. for 30 minutes and then allowed to warm to room temperature for 2 hours. The mixture was transferred to a large Erlenmeyer flask and the acid was neutralized by the careful addition of saturated aqueous sodium bicarbonate. The mixture was transferred to a separatory funnel and extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown semi-solid. The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3) to give 1.49 g (81%) of the title compound as a pink solid. MS (ESI−) m/z 178.0 (M−H); 1H NMR (DMSO-d6) δ 5.53 (br s, 2H), 6.77 (dd, J=9.2, 5.1 Hz, 1H), 7.13 (dd, J=9.2, 9.2 Hz, 1H). To an oven-dried, N2-purged 100-mL, round-bottomed flask containing a magnetic stir bar The flask was sealed with a septum to warm to room temperature for 2 hours The mixture was transferred to a separatory funnel extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over magnesium sulfate filtered concentrated by rotary evaporator to give a brown semi-solid The product was purified by flash chromatography (silica gel: 20% ethyl acetate, 80% hexanes, product Rf˜0.3)