2-TERT-BUTYL-1H-INDOLE

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

Procedure: To a solution of the mixture of 2-tert-butyl-2,3-dihydro-1H-indole and 2-tert-butyl-1H-indole (9.7 g ) in H2SO4 (98%, 80 mL) was slowly added KNO3 (5.6 g, 55.7 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1 h, carefully poured into cracked ice, basified with Na2CO3 to pH˜8 and extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography to give 2-tert-butyl-6-nitro-2,3-dihydro-1H-indole (4.0 g, 32% over 2 steps). at 0° C carefully poured into cracked ice extracted with ethyl acetate The combined extracts were washed with brine dried over anhydrous Na2SO4 concentrated under vacuum The residue was purified by column chromatography

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-dimethyl-N-o-tolyl-propionamide (30.0 g, 159 mmol) in dry THF (100 mL) was added dropwise n-BuLi (2.5 M, in hexane, 190 mL) at 15° C. The mixture was stirred overnight at 15° C., cooled in an ice-water bath and treated with saturated NH4Cl solution. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuum. The residue was purified by column chromatography to give 2-tert-butyl-1H-indole (23.8 g, 88%). cooled in an ice-water bath The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated in vacuum The residue was purified by column chromatography

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

Procedure: To a solution of the mixture of 2-tert-butyl-2,3-dihydro-1H-indole and 2-tert-butyl-1H-indole (9.7 g) in H2SO4 (98%, 80 mL) was slowly added KNO3 (5.6 g, 55.7 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1 h, carefully poured into cracked ice, basified with Na2CO3 to pH˜8 and extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography to give 2-tert-butyl-6-nitro-2,3-dihydro-1H-indole (4.0 g, 32% over 2 steps). at 0° C carefully poured into cracked ice extracted with ethyl acetate The combined extracts were washed with brine dried over anhydrous Na2SO4 concentrated under vacuum The residue was purified by column chromatography

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-dimethyl-N-o-tolyl-propionamide (30.0 g, 159 mmol) in dry THF (100 mL) was added dropwise n-BuLi (2.5 M, in hexane, 190 mL) at 15° C. The mixture was stirred overnight at 15° C., cooled in an ice-water bath and treated with saturated NH4Cl solution. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuum. The residue was purified by column chromatography to give 2-tert-butyl-1H-indole (23.8 g, 88%). cooled in an ice-water bath The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated in vacuum The residue was purified by column chromatography

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-tert-butyl-1H-indole (10 g, 48 mmol) in AcOH (40 mL) was added NaBH4 at 10° C. The mixture was stirred for 20 minutes at 10° C. before being treated dropwise with H2O under ice cooling. The mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under vacuum to give 2-tert-butylindoline (9.8 g), which was used directly in the next step. The mixture was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated under vacuum

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-tert-butyl-1H-indole (10 g, 48 mmol) in AcOH (40 mL) was added NaBH4 at 10° C. The mixture was stirred for 20 minutes at 10° C. before being treated dropwise with H2O under ice cooling. The mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under vacuum to give 2-tert-butylindoline (9.8 g), which was used directly in the next step. The mixture was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated under vacuum

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-o-tolylpivalamide (30.0 g, 159 mmol) in dry THF (100 mL) was added dropwise n-BuLi (2.5 M in hexane, 190 mL) at 15° C. After addition, the mixture was stirred overnight at 15° C. The mixture was cooled in an ice-water bath and treated with saturated NH4Cl. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuum. The residue was purified by column chromatography on silica gel to give 2-tert-butyl-1H-indole (24 g, 88%). 1H NMR (300 MHz, CDCl3) δ 7.99 (br. s, 1H), 7.54 (d, J=7.2 Hz, 1H), 7.05 (d, J=7.8 Hz, 1H), 7.06-7.13 (m, 2H), 6.26 (s, 1H), 1.39 (s, 9H). After addition The mixture was cooled in an ice-water bath The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated in vacuum The residue was purified by column chromatography on silica gel

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-tert-butyl-1H-indole (10 g, 48 mmol) in AcOH (40 mL) was added NaBH4 at 10° C. The mixture was stirred for 20 minutes at 10° C. before being treated dropwise with H2O under ice cooling. The mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under vacuum to give 2-tert-butylindoline (9.8 g), which was used directly in the next step. The mixture was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated under vacuum

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-o-tolylpivalamide (30.0 g, 159 mmol) in dry THE (100 mL) was added dropwise n-BuLi (2.5 M in hexane, 190 mL) at 15° C. After addition, the mixture was stirred overnight at 15° C. The mixture was cooled in an ice-water bath and treated with saturated NH4Cl. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuum. The residue was purified by column chromatography on silica gel to give 2-tert-butyl-1H-indole (24 g, 88%). 1H NMR (300 MHz, CDCl3) δ 7.99 (br. s, 1H), 7.54 (d, J=7.2 Hz, 1H), 7.05 (d, J=7.8 Hz, 1H), 7.06-7.13 (m, 2H), 6.26 (s, 1H), 1.39 (s, 9H). After addition The mixture was cooled in an ice-water bath The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated in vacuum The residue was purified by column chromatography on silica gel

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

Procedure: To a solution of the mixture of 2-tert-butyl-2,3-dihydro-1H-indole and 2-tert-butyl-1H-indole (9.7 g ) in H2SO4 (98%, 80 mL) was slowly added KNO3 (5.6 g, 55.7 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1 h, carefully poured into cracked ice, basified with Na2CO3 to pH˜8 and extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography to give 2-tert-butyl-6-nitro-2,3-dihydro-1H-indole (4.0 g, 32% over 2 steps). at 0° C carefully poured into cracked ice extracted with ethyl acetate The combined extracts were washed with brine dried over anhydrous Na2SO4 concentrated under vacuum The residue was purified by column chromatography

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-dimethyl-N-o-tolyl-propionamide (30.0 g, 159 mmol) in dry THF (100 mL) was added dropwise n-BuLi (2.5 M, in hexane, 190 mL) at 15° C. The mixture was stirred overnight at 15° C., cooled in an ice-water bath and treated with saturated NH4Cl solution. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuum. The residue was purified by column chromatography to give 2-tert-butyl-1H-indole (23.8 g, 88%). cooled in an ice-water bath The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated in vacuum The residue was purified by column chromatography

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-dimethyl-N-o-tolyl-propionamide (30.0 g, 159 mmol) in dry THF (100 mL) was added dropwise n-BuLi (2.5 M, in hexane, 190 mL) at 15° C. The mixture was stirred overnight at 15° C., cooled in an ice-water bath and treated with saturated NH4Cl solution. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuum. The residue was purified by column chromatography to give 2-tert-butyl-1H-indole (23.8 g, 88%). cooled in an ice-water bath The organic layer was separated the aqueous layer was extracted with ethyl acetate The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated in vacuum The residue was purified by column chromatography