4-(5-fluoro-1H-indol-3-yl)butan-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of 4-(5-fluoro-1H-indol-3-yl)-butan-2-one (11.1 g, 54.1 mmol) in THF (200 mL) at 0° C. is treated with MeMgBr (54.1 mL, 3 M in THF, 162.3 mmol) and stirred at 0° C. for 2 h, and warmed to rt overnight. The mixture is then poured over ice, treated with solid NH4Cl (3 g), and extracted with EtOAc (3×120 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-60% EtOAc in heptane to afford 4-(5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (3.07 g, 26%). MS: 222 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.94 (s, NH, 1H), 7.22 (m, 2H), 7.03 (s, 1H), 6.93 (m, 1H), 2.81 (m, 2H), 1.90 (m, 2H), 1.33 (s, 6H). warmed to rt overnight The mixture is then poured over ice extracted with EtOAc (3×120 mL) The combined organic layer is dried (Na2SO4) filtered concentrated in vacuo The residue is purified by silica gel chromatography eluting with 10%-60% EtOAc in heptane

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

Procedure: A solution of 4-(5-fluoro-1H-indol-3-yl)-butan-2-one (11.1 g, 54.1 mmol) in THF (200 mL) at 0° C. is treated with MeMgBr (54.1 mL, 3 M in THF, 162.3 mmol) and stirred at 0° C. for 2 h, and warmed to rt overnight. The mixture is then poured over ice, treated with solid NH4Cl (3 g), and extracted with EtOAc (3×120 mL). The combined organic layer is dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-60% EtOAc in heptane to afford 4-(5-fluoro-1H-indol-3-yl)-2-methyl-butan-2-ol (3.07 g, 26%). MS: 222 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.94 (s, NH, 1H), 7.22 (m, 2H), 7.03 (s, 1H), 6.93 (m, 1H), 2.81 (m, 2H), 1.90 (m, 2H), 1.33 (s, 6H). warmed to rt overnight The mixture is then poured over ice extracted with EtOAc (3×120 mL) The combined organic layer is dried (Na2SO4) filtered concentrated in vacuo The residue is purified by silica gel chromatography eluting with 10%-60% EtOAc in heptane

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

Procedure: A solution of 5-fluoroindole (10.5 g, 78 mmol) in MeCN (150 mL) at 0° C. is treated with methyl vinyl ketone (9.5 mL, 117 mmol) and Sc(OTf)3 (383 mg, 0.78 mmol) and stirred for 1 h. The mixture is then stirred an additional 6 h at rt. The mixture is concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-50% EtOAc in heptane to afford 4-(5-fluoro-1H-indol-3-yl)-butan-2-one (11.1 g, 70%). The mixture is then stirred an additional 6 h at rt The mixture is concentrated in vacuo The residue is purified by silica gel chromatography eluting with 10%-50% EtOAc in heptane

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

Procedure: A solution of 5-fluoroindole (10.5 g, 78 mmol) in MeCN (150 mL) at 0° C. is treated with methyl vinyl ketone (9.5 mL, 117 mmol) and Sc(OTf)3 (383 mg, 0.78 mmol) and stirred for 1 h. The mixture is then stirred an additional 6 h at rt. The mixture is concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-50% EtOAc in heptane to afford 4-(5-fluoro-1H-indol-3-yl)-butan-2-one (11.1 g, 70%). The mixture is then stirred an additional 6 h at rt The mixture is concentrated in vacuo The residue is purified by silica gel chromatography eluting with 10%-50% EtOAc in heptane