N-(3-chloro-4-fluorophenyl)propanamide

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

Procedure: The solid (10 g, 49.60 mmol) from step 1 dissolved in acetic acid (70 mL) was added with Br2 (12.7 mL, 247.93 mmol) dropwise for 2 h. Then the reaction mixture was kept stirring at rt for 5.5 h. The resulting mixture was poured to ice water (1 L) and quenched with excess of NaHSO3 until the solution became clear with yellow suspension. The quenched solution was filtered to get title compound (13.52 g, 97.2%). 1H NMR (400 MHz, DMSO-d6) δ 1.07 (t, J=7.6 Hz, 3H), 2.36 (q, J=7.6 Hz, 2H), 7.80 (d, J=7.6 Hz, 1H), 7.84 (d, J=8.8 Hz, 1H), 9.50 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 10.1, 29.3, 117.3, 117.4, 119.0, 119.2, 121.0, 121.2, 128.4, 134.45, 134.49, 153.4, 155.9, 173.0; quenched with excess of NaHSO3 until the solution The quenched solution was filtered

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

Procedure: 3-chloro-4-fluoroaniline (10 g, 67.32 mmol) dissolved in CH2Cl2 was added with propionyl chloride (6.6 mL, 74.10 mmol) and triethyl amine (10.2 mL, 73.58 mmol) dropwise under water bath, and the mixture was stirred for 2 h. The resulting solution was washed with water (2×50 mL) and saturated aqueous NaHCO3 solution (12 mL). The CH2Cl2 layer dried over MgSO4 was evaporated to give title compound as light purple solid (13.01 g, 96.3%). 1H NMR (400 MHz, DMSO-d6) δ 1.06 (t, J=7.6 Hz, 3H), 2.30 (q, J=7.6 Hz, 2H), 7.31 (dd, J=9.2 and 8.8 Hz, 1H), 7.44 (ddd, J=8.8 and 4 and 2.8 Hz, 1H), 7.91 (dd, J=7.2 and 2.8 Hz, 1H), 10.04 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 9.4, 29.4, 116.6, 116.8, 118.8, 119.0, 119.1, 120.2, 136.55, 136.58, 151.5, 153.9, 172.1; The resulting solution was washed with water (2×50 mL) and saturated aqueous NaHCO3 solution (12 mL) The CH2Cl2 layer dried over MgSO4 was evaporated

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

Procedure: 3-chloro-4-fluoroaniline (10 g, 67.32 mmol) dissolved in CH2Cl2 was added with propionyl chloride (6.6 mL, 74.10 mmol) and triethyl amine (10.2 mL, 73.58 mmol) dropwise under water bath, and the mixture was stirred for 2 h. The resulting solution was washed with water (2×50 mL) and saturated aqueous NaHCO3 solution (12 mL). The CH2Cl2 layer dried over MgSO4 was evaporated to give title compound as light purple solid (13.01 g, 96.3%). 1H NMR (400 MHz, DMSO-d6) δ 1.06 (t, J=7.6 Hz, 3H), 2.30 (q, J=7.6 Hz, 2H), 7.31 (dd, J=9.2 and 8.8 Hz, 1H), 7.44 (ddd, J=8.8 and 4 and 2.8 Hz, 1H), 7.91 (dd, J=7.2 and 2.8 Hz, 1H), 10.04 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 9.4, 29.4, 116.6, 116.8, 118.8, 119.0, 119.1, 120.2, 136.55, 136.58, 151.5, 153.9, 172.1; The resulting solution was washed with water (2×50 mL) and saturated aqueous NaHCO3 solution (12 mL) The CH2Cl2 layer dried over MgSO4 was evaporated

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

Procedure: The solid (10 g, 49.60 mmol) from step 1 dissolved in acetic acid (70 mL) was added with Br2 (12.7 mL, 247.93 mmol) dropwise for 2 h. Then the reaction mixture was kept stirring at rt for 5.5 h. The resulting mixture was poured to ice water (1 L) and quenched with excess of NaHSO3 until the solution became clear with yellow suspension. The quenched solution was filtered to get title compound (13.52 g, 97.2%). 1H NMR (400 MHz, DMSO-d6) δ 1.07 (t, J=7.6 Hz, 3H), 2.36 (q, J=7.6 Hz, 2H), 7.80 (d, J=7.6 Hz, 1H), 7.84 (d, J=8.8 Hz, 1H), 9.50 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 10.1, 29.3, 117.3, 117.4, 119.0, 119.2, 121.0, 121.2, 128.4, 134.45, 134.49, 153.4, 155.9, 173.0; quenched with excess of NaHSO3 until the solution The quenched solution was filtered

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

Procedure: 3-chloro-4-fluoroaniline (10 g, 67.32 mmol) dissolved in CH2Cl2 was added with propionyl chloride (6.6 mL, 74.10 mmol) and triethyl amine (10.2 mL, 73.58 mmol) dropwise under water bath, and the mixture was stirred for 2 h. The resulting solution was washed with water (2×50 mL) and saturated aqueous NaHCO3 solution (12 mL). The CH2Cl2 layer dried over MgSO4 was evaporated to give title compound as light purple solid (13.01 g, 96.3%). 1H NMR (400 MHz, DMSO-d6) δ 1.06 (t, J=7.6 Hz, 3H), 2.30 (q, 7.6 Hz, 2H) 7.31 (dd, J=9.2 and 8.8 Hz, 1H), 7.44 (ddd, J=8.8 and 4 and 2.8 Hz, 1H), 7.91 (dd, J=7.2 and 2.8 Hz, 1H), 10.04 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 9.4, 29.4, 116.6, 116.8, 118.8, 119.0, 119.1, 120.2, 136.55, 136.58, 151.5, 153.9, 172.1; The resulting solution was washed with water (2×50 mL) and saturated aqueous NaHCO3 solution (12 mL) The CH2Cl2 layer dried over MgSO4 was evaporated

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

Procedure: The solid (10 g, 49.60 mmol) from step 1 dissolved in acetic acid (70 mL) was added with Br2 (12.7 mL, 247.93 mmol) dropwise for 2 h. Then the reaction mixture was kept stirring at rt for 5.5 h. The resulting mixture was poured to ice water (1 L) and quenched with excess of NaHSO3 until the solution became clear with yellow suspension. The quenched solution was filtered to get title compound (13.52 g, 97.2%). 1H NMR (400 MHz, DMSO-d6) δ 1.07 (t, J=7.6 Hz, 3H), 2.36 (q, J=7.6 Hz, 2H), 7.80 (d, J=7.6 Hz, 1H), 7.84 (d, J=8.8 Hz, 1H), 9.50 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 10.1, 29.3, 117.3, 117.4, 119.0, 119.2, 121.0, 121.2, 128.4, 134.45, 134.49, 153.4, 155.9, 173.0; quenched with excess of NaHSO3 until the solution The quenched solution was filtered

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

Procedure: 3-chloro-4-fluoroaniline (10 g, 67.32 mmol) dissolved in CH2Cl2 was added with propionyl chloride (6.6 mL, 74.10 mmol) and triethyl amine (10.2 mL, 73.58 mmol) dropwise under water bath, and the mixture was stirred for 2 h. The resulting solution was washed with water (2×50 mL) and saturated aqueous NaHCO3 solution (12 mL). The CH2Cl2 layer dried over MgSO4 was evaporated to give title compound as light purple solid (13.01 g, 96.3%). 1H NMR (400 MHz, DMSO-d6) δ 1.06 (t, J=7.6 Hz, 3H), 2.30 (q, J=7.6 Hz, 2H), 7.31 (dd, J=9.2 and 8.8 Hz, 1H), 7.44 (ddd, J=8.8 and 4 and 2.8 Hz, 1H), 7.91 (dd, J=7.2 and 2.8 Hz, 1H), 10.04 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 9.4, 29.4, 116.6, 116.8, 118.8, 119.0, 119.1, 120.2, 136.55, 136.58, 151.5, 153.9, 172.1; The resulting solution was washed with water (2×50 mL) and saturated aqueous NaHCO3 solution (12 mL) The CH2Cl2 layer dried over MgSO4 was evaporated