2-methyl-N-(2-methylphenyl)aniline

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a reaction vessel were combined di(2-tolyl)amine (11.7 g, 59.3 mmol), elemental sulfur (3.9 g, 121.65 mmol, 2 eq.), crushed iodine (0.44 g, 1.73 mmol, 3 mol %) followed by o-dichlorobenzene (22 mL). Added an outlet to a dilute bleach solution (for hydrogen sulfide evolution) then put under argon. Refluxed at 180° C. for 4 h and removed solvent under reduced pressure. Purified by column chromatography with 2.0% ethyl acetate/98% hexane to obtain the desired product as white crystals (2 g, 8.8 mmol, 15% yield). Alternatively, the reaction was cooled to about 60° C. then hexane was added for extraction. Repeated hot hexane extractions of reaction until the product was no longer obtained in residue (about four times). Combined hexane extractions and concentrated in vacuo. Purified resulting residue either through repeated hot acetone/isopropanol crystallizations (or triturations) or flash column chromatography using 2% ethyl acetate/98% hexane to obtain product as white crystals (2.92 g, 12.8 mmol, 28% yield). To a reaction vessel were combined removed solvent under reduced pressure Purified by column chromatography with 2.0% ethyl acetate/98% hexane

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

Procedure: A round-bottom flask was heated, and then allow to cool to room temperature under argon. To the flask were added Pd2(dba)3 (1.39 g, 1.52 mmol, 1.0 mol %) or Pd(dba)2 (1.38 g, 2.4 mmol, 1.4 mol %), 2-(di-tert-butylphosphino)biphenyl (1.09 g, 3.65 mmol, 2.4 mol %), 2-bromotoluene (12, 40 mL, 332.1 mmol) or 2-chlorotoluene (39 mL, 332.1 mmol), lithium amide (3.47 g, 151.1 mmol, 45 mol %), sodium t-butoxide 29.5 g, 297.7 mmol, 90 mol %), then toluene (150 mL). The reaction mixture was heated at 80° C. under argon overnight, then allowed to cool to room temperature. The resulting liquid was diluted with diethyl ether, and then filtered through a pad of celite. The resulting cocnentrte was filtered in vacuo and used in the next reaction without purification. The crude material was purified by column chromatography with hexane to give the product as white crystals with a yellow tint (23.4 g, 118.6 mmol, 72% yield). A round-bottom flask was heated The reaction mixture was heated at 80° C. under argon overnight to cool to room temperature filtered through a pad of celite The resulting cocnentrte was filtered in vacuo used in the next reaction without purification The crude material was purified by column chromatography with hexane

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a reaction vessel were combined di(2-tolyl)amine (11.7 g, 59.3 mmol), elemental sulfur (3.9 g, 121.65 mmol, 2 eq.), crushed iodine (0.44 g, 1.73 mmol, 3 mol %) followed by o-dichlorobenzene (22 mL). Added an outlet to a dilute bleach solution (for hydrogen sulfide evolution) then put under argon. Refluxed at 180° C. for 4 h and removed solvent under reduced pressure. Purified by column chromatography with 2.0% ethyl acetate/98% hexane to obtain the desired product as white crystals (2 g, 8.8 mmol, 15% yield). Alternatively, the reaction was cooled to about 60° C. then hexane was added for extraction. Repeated hot hexane extractions of reaction until the product was no longer obtained in residue (about four times). Combined hexane extractions and concentrated in vacuo. Purified resulting residue either through repeated hot acetone/isopropanol crystallizations (or triturations) or flash column chromatography using 2% ethyl acetate/98% hexane to obtain product as white crystals (2.92 g, 12.8 mmol, 28% yield). To a reaction vessel were combined removed solvent under reduced pressure Purified by column chromatography with 2.0% ethyl acetate/98% hexane

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

Procedure: A round-bottom flask was heated, and then allow to cool to room temperature under argon. To the flask were added Pd2(dba)3 (1.39 g, 1.52 mmol, 1.0 mol %) or Pd(dba)2 (1.38 g, 2.4 mmol, 1.4 mol %), 2-(di-tert-butylphosphino)biphenyl (1.09 g, 3.65 mmol, 2.4 mol %), 2-bromotoluene (12, 40 mL, 332.1 mmol) or 2-chlorotoluene (39 mL, 332.1 mmol), lithium amide (3.47 g, 151.1 mmol, 45 mol %), sodium t-butoxide 29.5 g, 297.7 mmol, 90 mol %), then toluene (150 mL). The reaction mixture was heated at 80° C. under argon overnight, then allowed to cool to room temperature. The resulting liquid was diluted with diethyl ether, and then filtered through a pad of celite. The resulting cocnentrte was filtered in vacuo and used in the next reaction without purification. The crude material was purified by column chromatography with hexane to give the product as white crystals with a yellow tint (23.4 g, 118.6 mmol, 72% yield). A round-bottom flask was heated The reaction mixture was heated at 80° C. under argon overnight to cool to room temperature filtered through a pad of celite The resulting cocnentrte was filtered in vacuo used in the next reaction without purification The crude material was purified by column chromatography with hexane

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

Procedure: A round-bottom flask was heated, and then allow to cool to room temperature under argon. To the flask were added Pd2(dba)3 (1.39 g, 1.52 mmol, 1.0 mol %) or Pd(dba)2 (1.38 g, 2.4 mmol, 1.4 mol %), 2-(di-tert-butylphosphino)biphenyl (1.09 g, 3.65 mmol, 2.4 mol %), 2-bromotoluene (12, 40 mL, 332.1 mmol) or 2-chlorotoluene (39 mL, 332.1 mmol), lithium amide (3.47 g, 151.1 mmol, 45 mol %), sodium t-butoxide 29.5 g, 297.7 mmol, 90 mol %), then toluene (150 mL). The reaction mixture was heated at 80° C. under argon overnight, then allowed to cool to room temperature. The resulting liquid was diluted with diethyl ether, and then filtered through a pad of celite. The resulting cocnentrte was filtered in vacuo and used in the next reaction without purification. The crude material was purified by column chromatography with hexane to give the product as white crystals with a yellow tint (23.4 g, 118.6 mmol, 72% yield). A round-bottom flask was heated The reaction mixture was heated at 80° C. under argon overnight to cool to room temperature filtered through a pad of celite The resulting cocnentrte was filtered in vacuo used in the next reaction without purification The crude material was purified by column chromatography with hexane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,7-dibromo-9,9-dimethyl-9H-fluorene (31.64 g, 89.87 mmol), ditolylamine (8.865 g, 44.9 mmol), Pd(dppf)Cl2 (1.644 g, 2.25 mmol) and sodium tert-butoxide (10.796 g, 112.3 mmol) in toluene 400 mL was degassed and heated at about 80° C. overnight. The resulting mixture was poured into ethyl acetate (500 mL). After the precipitate was filtered off, the solution was washed with water and brine, dried over Na2SO4, loaded on silica gel and purified by flash column (hexane to hexanes/dichloromethane 99:1 to 95:5 gradients). After removal of solvent and recrystallization in dichloromethane/hexanes, a white solid (Compound 32) was obtained (14.0169 g, in 66.6% yield). was degassed The resulting mixture was poured into ethyl acetate (500 mL) After the precipitate was filtered off the solution was washed with water and brine dried over Na2SO4 purified by flash column (hexane to hexanes/dichloromethane 99:1 to 95:5 gradients) After removal of solvent and recrystallization in dichloromethane/hexanes

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The following were added to a reaction vessel dried as indicated: One mole percent of Pd2(dba)3 (1.39 g, 1.52 mmol) or Pd(dba)2 (1.38 g, 2.4 mmol, 1.4 mol %), 2-(di-tert-butylphosphino)biphenyl (1.09 g, 3.65 mmoles, 2.4 mole %), 2-bromotoluene (40 mL, 332.1 mmol) or 2-chlorotoluene (39 mL, 332.1 mmol), lithium amide (3.47 g, 151.1 mmol, 45 mol %), sodium t-butoxide 29.5 g, 297.7 mmol, 90 mol %), and then toluene (150 mL). The mixture was then heated at 80° C. under argon overnight. Following the reaction period the mixture was allowed to cool to room temperature, and then diluted with diethyl ether and filtered through a pad of celite. The collected filtrate was concentrated in vacuo. Purify of the resulting residue was accomplished by flash silica gel chromatography in hexane to give the desired product as white crystals with a yellow tint (23.4 g, 118.6 mmol, 72% yield). The following were added to a reaction vessel dried the reaction period the mixture to cool to room temperature filtered through a pad of celite The collected filtrate was concentrated in vacuo Purify of the resulting residue

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The following were added to a reaction vessel dried as indicated: One mole percent of Pd2(dba)3 (1.39 g, 1.52 mmol) or Pd(dba)2 (1.38 g, 2.4 mmol, 1.4 mol %), 2-(di-tert-butylphosphino)biphenyl (1.09 g, 3.65 mmoles, 2.4 mole %), 2-bromotoluene (40 mL, 332.1 mmol) or 2-chlorotoluene (39 mL, 332.1 mmol), lithium amide (3.47 g, 151.1 mmol, 45 mol %), sodium t-butoxide 29.5 g, 297.7 mmol, 90 mol %), and then toluene (150 mL). The mixture was then heated at 80° C. under argon overnight. Following the reaction period the mixture was allowed to cool to room temperature, and then diluted with diethyl ether and filtered through a pad of celite. The collected filtrate was concentrated in vacuo. Purify of the resulting residue was accomplished by flash silica gel chromatography in hexane to give the desired product as white crystals with a yellow tint (23.4 g, 118.6 mmol, 72% yield). The following were added to a reaction vessel dried the reaction period the mixture to cool to room temperature filtered through a pad of celite The collected filtrate was concentrated in vacuo Purify of the resulting residue

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The following were added to a reaction vessel dried as indicated: One mole percent of Pd2(dba)3 (1.39 g, 1.52 mmol) or Pd(dba)2 (1.38 g, 2.4 mmol, 1.4 mol %), 2-(di-tert-butylphosphino)biphenyl (1.09 g, 3.65 mmoles, 2.4 mole %), 2-bromotoluene (40 mL, 332.1 mmol) or 2-chlorotoluene (39 mL, 332.1 mmol), lithium amide (3.47 g, 151.1 mmol, 45 mol %), sodium t-butoxide 29.5 g, 297.7 mmol, 90 mol %), and then toluene (150 mL). The mixture was then heated at 80° C. under argon overnight. Following the reaction period the mixture was allowed to cool to room temperature, and then diluted with diethyl ether and filtered through a pad of celite. The collected filtrate was concentrated in vacuo. Purify of the resulting residue was accomplished by flash silica gel chromatography in hexane to give the desired product as white crystals with a yellow tint (23.4 g, 118.6 mmol, 72% yield). The following were added to a reaction vessel dried the reaction period the mixture to cool to room temperature filtered through a pad of celite The collected filtrate was concentrated in vacuo Purify of the resulting residue

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

Procedure: The round-bottom flask was heated then allow to cool to room temperature under argon. Added Pd2(dba)3 (1.39 g, 1.52 mmol, 1.0 mol %) or Pd(dba)2 (1.38 g, 2.4 mmol, 1.4 mol %), 2-(di-tert-butylphosphino)biphenyl (1.09 g, 3.65 mmol, 2.4 mol %), 2-bromotoluene (40 mL, 332.1 mmol) or 2-chlorotoluene (39 mL, 332.1 mmol), lithium amide (3.47 g, 151.1 mmol, 45 mol %), sodium t-butoxide (29.5 g, 297.7 mmol, 90 mol %), followed by toluene (150 mL). The reaction mixture was heated at 80° C. under argon overnight, then allowed to cool to room temperature. Diluted with diethyl ether then filtered through a pad of Celite. Concentrated the resulting filtrate in vacuo. Used the crude material in the next reaction without purification. (Crude material can be purified by flash chromatography with hexane which gave the product as white crystals with a yellow tint (23.4 g, 118.6 mmol, 72% yield)). The round-bottom flask was heated The reaction mixture was heated at 80° C. under argon overnight to cool to room temperature then filtered through a pad of Celite Concentrated the resulting filtrate in vacuo in the next reaction without purification (Crude material can be purified by flash chromatography with hexane which

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of di-o-tolylamine (Compound 9) (6.00 g, 30.4 mmol), iodobenzene (12.2 g, 60 mmol), Pd(OAc)2 (0.34 g, 1.5 mmol), P(t-Bu)3 (0.6 g, 3 mmol), sodium tert-butoxide (5.76 g, 60 mmol) in toluene (120 mL) was degassed and heated at about 120° C. for 40 hours. The resulting mixture was diluted with ethyl acetate (200 mL), washed with brine, dried over Na2SO4, loaded on silica gel and purified by flash column using eluents of hexanes to give a white solid (Compound 10) (8.2 g, in 98% yield). was degassed The resulting mixture was diluted with ethyl acetate (200 mL) washed with brine dried over Na2SO4 purified by flash column

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of o-toluidine (6.05 g, 56.5 mmol), 1-bromo-2-methylbenzene (8.5 g, 50 mmol), Pd(dppf)Cl2 and sodium tert-butoxide (9.6 g, 0.1 mmol) in toluene (120 mL) was degassed and heated at about 100° C. overnight. The mixture was purified by flash column using eluents of hexanes/dichloromethane 2:1 to give a white solid (Compound 9) (8.84 g, in 89.7% yield). was degassed The mixture was purified by flash column