2,2,2-trifluoro-N-(2-methylphenyl)acetamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 16.43 mL (5.00 equiv.) Chlorosulfonic acid was cooled in an aceton/ice-bath and 10.00 g 2,2,2-trifluoro-N-o-tolyl-acetamide was added in three portions, keeping the reaction mixture temperature below 5° C. The ice-bath was removed, the pale yellow mixture was allowed to warm to room temperature and then heated on an oil bath of 70° C. for 5.5 hours. The oil bath was removed and at about 30-35° C. the brown mixture was poured very carefully into a beaker with ice (exotermic, copious amounts of HCl evolve), giving a thick, gummy and very sticky precipitate. The mixture was extracted three times with DCM and the combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated onto silica. Purification with flash chromatography (EtOAc/PA 1:9→1:4) yielded 10.3 g (69%) of a white solid. 1H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 7.90 (br.s., 1H), 7.94 (s, 1H), 7.98 (dd, J=8.6, 2.15 Hz, 1H), 8.35 (d, J=8.6 Hz, 1H). the reaction mixture temperature below 5° C The ice-bath was removed heated on an oil bath of 70° C. for 5.5 hours The oil bath was removed and at about 30-35° C. the brown mixture was poured very carefully into a beaker with ice (exotermic, copious amounts of HCl evolve) giving a thick, gummy and very sticky precipitate The mixture was extracted three times with DCM the combined organic layers were washed with brine dried over Na2SO4 filtered evaporated onto silica Purification with flash chromatography (EtOAc/PA 1:9→1:4)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2,2-trifluoro-N-o-tolylacetamide (5.0 g; 24.6 mmol) was dissolved in 20 mL CS2. The mixture was cooled below 10° C. Bromoacetic bromide (10.1 g; 50.0 mmol) was added dropwise. AlCl3 (10.0 g; 75.0 mmol) was added in portions, with drying tube attached to the reaction flask. The reaction mixture was refluxed overnight. After the reaction is complete as monitored by TLC, the upper CS2 layer was removed. The lower layer was added into 7.0 mL ice water mixed with HCl. The product was extracted into CH2Cl2, and dried over MgSO4. The solvent was removed, and the solid was dried to afford 5.0 g of crude product, which was purified by silica gel column chromatography, to afford 3.0 g (yield 38%) of product as yellow solid. 1H NMR (300 MHz; CDCl3), δ 8.40 (s, 1H, Ar—H), 7.87 (brs+d, 3JHH=8.0 Hz, 2H, Ar—H), 7.43 (d, 3JHH=8.0 Hz, 1H, Ar—H), 4.46 (s, 2H, COCH2Br), 2.41 (s, 3H, CH3). The mixture was cooled below 10° C with drying tube The reaction mixture was refluxed overnight the upper CS2 layer was removed The lower layer was added into 7.0 mL ice water mixed with HCl The product was extracted into CH2Cl2 dried over MgSO4 The solvent was removed the solid was dried to afford 5.0 g of crude product, which was purified by silica gel column chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2,2-trifluoro-N-o-tolylacetamide (5.0 g; 24.6 mmol) was dissolved in 20 mL CS2. The mixture was cooled below 10° C. Bromoacetic bromide (10.1 g; 50.0 mmol) was added dropwise. AlCl3 (10.0 g; 75.0 mmol) was added in portions, with drying tube attached to the reaction flask. The reaction mixture was refluxed overnight. After the reaction is complete as monitored by TLC, the upper CS2 layer was removed. The lower layer was added into 7.0 mL ice water mixed with HCl. The product was extracted into CH2Cl2, and dried over MgSO4. The solvent was removed, and the solid was dried to afford 5.0 g of crude product, which was purified by silica gel column chromatography, to afford 3.0 g (yield 38%) of product as yellow solid. 1H NMR (300 MHz; CDCl3), δ 8.40 (s, 1H, Ar—H), 7.87 (brs+d, 3JHH=8.0 Hz, 2H, Ar—H), 7.43 (d, 3JHH=8.0 Hz, 1H, Ar—H), 4.46 (s, 2H, COCH2Br), 2.41 (s, 3H, CH3). The mixture was cooled below 10° C with drying tube The reaction mixture was refluxed overnight the upper CS2 layer was removed The lower layer was added into 7.0 mL ice water mixed with HCl The product was extracted into CH2Cl2 dried over MgSO4 The solvent was removed the solid was dried to afford 5.0 g of crude product, which was purified by silica gel column chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2,2-trifluoro-N-o-tolylacetamide (8.0 g; 39.4 mmol) was dissolved in 20 mL CS2. Bromoacetic bromide (8.4 g; 68.3 mmol) was added dropwise. AlCl3 (16.0 g; 120 mmol) was added in portions, with drying tube attached to the reaction flask. The reaction mixture was refluxed overnight. After reaction, the solvent was removed. Ice and water were added, and some yellow solid precipitated. The solid was isolated by filtration, and purified by silica gel column chromatography, to afford 3.8 g (yield 39%) of product as off-white solid. 1H NMR (300 MHz; CDCl3), δ 8.30 (s, 1H, Ar—H), 7.91 (brs, 1H, NH), 7.81 (d, 3JHH=8.2 Hz, 1H, Ar—H), 7.36 (d, 3JHH=7.9 Hz, 1H, Ar—H), 2.60 (s, 3H, COCH3), 2.36 (s, 3H, CH3). with drying tube The reaction mixture was refluxed overnight After reaction the solvent was removed Ice and water were added some yellow solid precipitated The solid was isolated by filtration purified by silica gel column chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 16.43 mL (5.00 equiv.) Chlorosulfonic acid was cooled in an aceton/ice-bath and 10.00 g 2,2,2-trifluoro-N-o-tolyl-acetamide was added in three portions, keeping the reaction mixture temperature below 5° C. The ice-bath was removed, the pale yellow mixture was allowed to warm to room temperature and then heated on an oil bath of 70° C. for 5.5 hours. The oil bath was removed and at about 30-35° C. the brown mixture was poured very carefully into a beaker with ice (exotermic, copious amounts of HCl evolve), giving a thick, gummy and very sticky precipitate. The mixture was extracted three times with DCM and the combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated onto silica. Purification with flash chromatography (EtOAc/PA 1:9→1:4) yielded 10.3 g (69%) of a white solid. 1H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 7.90 (br.s., 1H), 7.94 (s, 1H), 7.98 (dd, J=8.6, 2.15 Hz, 1H), 8.35 (d, J=8.6 Hz, 1H). the reaction mixture temperature below 5° C The ice-bath was removed heated on an oil bath of 70° C. for 5.5 hours The oil bath was removed and at about 30-35° C. the brown mixture was poured very carefully into a beaker with ice (exotermic, copious amounts of HCl evolve) giving a thick, gummy and very sticky precipitate The mixture was extracted three times with DCM the combined organic layers were washed with brine dried over Na2SO4 filtered evaporated onto silica Purification with flash chromatography (EtOAc/PA 1:9→1:4)

反応条件: temp:155.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Synthesized according to general procedure 69. A mixture of 2,2,2-trifluoro-N-o-tolylacetamide (6.3 gm, 31 mmol) and chlorosulfonic acid (10.3 mL, 155 mmol) was heated at 155° C. for 15 min. After cooling to RT, the mixture was poured into ice water and extracted with EtOAc. The organic layer was concentrated and purified via silica gel chromatography using 0-25% EtOAc in hexanes gave 3-methyl-4-(2,2,2-trifluoroacetamido)benzene-1-sulfonyl chloride (7.8 g, 85%). 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.46 (dd, J=8.1, 1.8 Hz, 1H), 7.21 (dd, J=8.1, 2.9 Hz, 1H), 2.18 (s, 3H). Synthesized After cooling to RT extracted with EtOAc The organic layer was concentrated purified via silica gel chromatography

反応条件: temp:155.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Synthesized according to general procedure 69. A mixture of 2,2,2-trifluoro-N-o-tolylacetamide (6.3 gm, 31 mmol) and chlorosulfonic acid (10.3 mL, 155 mmol) was heated at 155° C. for 15 min. After cooling to RT, the mixture was poured into ice water and extracted with EtOAc. The organic layer was concentrated and purified via silica gel chromatography using 0-25% EtOAc in hexanes gave 3-methyl-4-(2,2,2-trifluoroacetamido)benzene-1-sulfonyl chloride (7.8 g, 85%). 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.46 (dd, J=8.1, 1.8 Hz, 1H), 7.21 (dd, J=8.1, 2.9 Hz, 1H), 2.18 (s, 3H). Synthesized After cooling to RT extracted with EtOAc The organic layer was concentrated purified via silica gel chromatography

反応条件: temp:155.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Synthesized according to general procedure 69. A mixture of 2,2,2-trifluoro-N-o-tolylacetamide (6.3 gm, 31 mmol) and chlorosulfonic acid (10.3 mL, 155 mmol) was heated at 155° C. for 15 min. After cooling to RT, the mixture was poured into ice water and extracted with EtOAc. The organic layer was concentrated and purified via silica gel chromatography using 0-25% EtOAc in hexanes gave 3-methyl-4-(2,2,2-trifluoroacetamido)benzene-1-sulfonyl chloride (7.8 g, 85%). 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.46 (dd, J=8.1, 1.8 Hz, 1H), 7.21 (dd, J=8.1, 2.9 Hz, 1H), 2.18 (s, 3H). Synthesized After cooling to RT extracted with EtOAc The organic layer was concentrated purified via silica gel chromatography

反応条件: temp:155.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Synthesized according to general procedure 69. A mixture of 2,2,2-trifluoro-N-o-tolylacetamide (6.3 gm, 31 mmol) and chlorosulfonic acid (10.3 mL, 155 mmol) was heated at 155° C. for 15 min. After cooling to RT, the mixture was poured into ice water and extracted with EtOAc. The organic layer was concentrated and purified via silica gel chromatography using 0-25% EtOAc in hexanes gave 3-methyl-4-(2,2,2-trifluoroacetamido)benzene-1-sulfonyl chloride (7.8 g, 85%). 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.46 (dd, J=8.1, 1.8 Hz, 1H), 7.21 (dd, J=8.1, 2.9 Hz, 1H), 2.18 (s, 3H). Synthesized After cooling to RT extracted with EtOAc The organic layer was concentrated purified via silica gel chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 16.43 mL (5.00 equiv.) Chlorosulfonic acid was cooled in an aceton/ice-bath and 10.00 g 2,2,2-trifluoro-N-o-tolyl-acetamide was added in three portions, keeping the reaction mixture temperature below 5° C. The ice-bath was removed, the pale yellow mixture was allowed to warm to room temperature and then heated on an oil bath of 70° C. for 5.5 hours. The oil bath was removed and at about 30-35° C. the brown mixture was poured very carefully into a beaker with ice (exotermic, copious amounts of HCl evolve), giving a thick, gummy and very sticky precipitate. The mixture was extracted three times with DCM and the combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated onto silica. Purification with flash chromatography (EtOAc/PA 1:9→1:4) yielded 10.3 g (69%) of a white solid. 1H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 7.90 (br.s., 1H), 7.94 (s, 1H), 7.98 (dd, J=8.6, 2.15 Hz, 1H), 8.35 (d, J=8.6 Hz, 1H). the reaction mixture temperature below 5° C The ice-bath was removed heated on an oil bath of 70° C. for 5.5 hours The oil bath was removed and at about 30-35° C. the brown mixture was poured very carefully into a beaker with ice (exotermic, copious amounts of HCl evolve) giving a thick, gummy and very sticky precipitate The mixture was extracted three times with DCM the combined organic layers were washed with brine dried over Na2SO4 filtered evaporated onto silica Purification with flash chromatography (EtOAc/PA 1:9→1:4)