(2-ethylphenyl)hydrazine

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

Procedure: This material can be prepared from (1S)-1-ethyl-2-oxo-4-(phenylmethyl)cyclohexaneacetic acid methyl ester as described in Example 2, Step (b), for racemic material by substituting phenylhydrazine for 2-ethylphenylhydrazine.

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

Procedure: This material can be prepared from (1S)-1-ethyl-2-oxo-4-(phenylmethyl)cyclohexaneacetic acid methyl ester as described in Example 2, Step (b), for racemic material by substituting phenylhydrazine for 2-ethylphenylhydrazine.

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

Procedure: A solution of 1-ethyl-4-(5-hexenyl)-2-oxocyclohexaneacetic acid methyl ester isomer B (4.24 g, 15.14 mmol) and 2-ethylphenylhydrazine (2.27 g, 16.7 mmol) in 30.3 mL of toluene was refluxed under nitrogen for 22 hours with azeotropic removal of water. The toluene was then removed in vacuo and replaced with 10.8 mL of acetic acid. The solution was treated with borontrifluoride etherate (2.79 g, 19.7 mmol, 2.42 mL) and refluxed for 20 minutes under nitrogen. The reaction mixture was poured into 120 mL of water and extracted with 4×80 mL of ether. The pooled extracts were washed with 2×110 mL of 1M HCl and 2×80 mL of 2.5N NaOH. Drying (MgSO4) and flash chromatography (75 mm diameter column, 8% ethyl acetate in petroleum ether eluent) afforded 3.72 g (9.73 mmol, 64%) of 1,8-diethyl-4-(5-hexenyl)-2,3,4,9-tetrahydro-1H-carbazole-1 -acetic acid methyl ester. Of this, 3.68 g (9.66 mmol) were refluxed in a solution of ethanol (30.9 mL) and 2.5N NaOH (7.7 mL) for 45 minutes under nitrogen. The ethanol was then removed in vacuo and the residue was suspended in 120 mL of 1N HCl. It was extracted with 4×40 mL of ether and the pooled extracts were dried over MgSO4. Flash chromatography (50 mm diameter column, 10% ethyl acetate in petroleum ether eluent, 2% H3PO4 in MeOH treated silica gel) afforded 3.41 g (9.18 mmol, 95%) of a light yellow solid which was recrystallized from 85:15 petroleum ether:benzene. This resulted in 1.98 g of a white powder which were dried at 84° C. for 31 hours followed by recrystallization from 85:15 petroleum ether:benzene once again. Drying at 84° C. for 24 hours resulted in 1.41 g of a white powder, m.p. 96°-97° C. The toluene was then removed in vacuo refluxed for 20 minutes under nitrogen extracted with 4×80 mL of ether The pooled extracts were washed with 2×110 mL of 1M HCl and 2×80 mL of 2.5N NaOH Drying (MgSO4) and flash chromatography (75 mm diameter column, 8% ethyl acetate in petroleum ether eluent)

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

Procedure: The more polar ketone isomer of 2-carbomethoxymethyl-5-ethenyl-2-ethylcyclohexanone (5.084 g, 22.66 mmol) and the 2-ethylphenylhydrazine (3.086 g, 22.66 mmol) were heated at reflux in 97 ml of methanol under nitrogen for 48 hours. The reaction was then cooled to 0° C., treated with 45.32 mmol (3.56 g, 3.22 ml) of AcCl and refluxed an additional 45 minutes. Cooling, concentration and flash chromatography afforded 2.772 g (8.52 mmol, 38%) of indole as an orange oil. Rf =0.47 in 15% ethyl acetate/petroleum ether on TLC. refluxed an additional 45 minutes Cooling concentration and flash chromatography

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

Procedure: The more polar ketone isomer of 2-carbomethoxymethyl-5-ethenyl-2-ethylcyclohexanone (5.084 g, 22.66 mmol) and the 2-ethylphenylhydrazine (3.086 g, 22.66 mmol) were heated at reflux in 97 ml of methanol under nitrogen for 48 hours. The reaction was then cooled to 0° C., treated with 45.32 mmol (3.56 g, 3.22 ml) of AcCl and refluxed an additional 45 minutes. Cooling, concentration and flash chromatography afforded 2.772 g (8.52 mmol, 38%) of indole as an orange oil. Rf =0.47 in 15% ethyl acetate/petroleum ether on TLC. refluxed an additional 45 minutes Cooling concentration and flash chromatography

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

Procedure: A solution of 1-ethyl-4-(5-hexenyl)-2-oxocyclohexaneacetic acid methyl ester isomer B (4.24 g, 15.14 mmol) and 2-ethylphenylhydrazine (2.27 g, 16.7 mmol) in 30.3 mL of toluene was refluxed under nitrogen for 22 hours with azeotropic removal of water. The toluene was then removed in vacuo and replaced with 10.8 mL of acetic acid. The solution was treated with borontrifluoride etherate (2.79 g, 19.7 mmol, 2.42 mL) and refluxed for 20 minutes under nitrogen. The reaction mixture was poured into 120 mL of water and extracted with 4×80 mL of 2.5N NaOH. Drying (MgSO4) and flash chromatography (75 mm diameter column, 8% ethyl acetate in petroleum ether eluent) afforded 3.72 g (9.73 mmol, 64%) of 1,8-diethyl-4-(5-hexenyl)-2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid methyl ester. Of this, 3.68 g (9.66 mmol) were refluxed in a solution of ethanol (30.9 mL) and 2.5N NaOH (7.7 mL) for 45 minutes under nitrogen. The ethanol was then removed in vacuo and the residue was suspended in 120 mL of 1N HCl. It was extracted with 4×40 mL of ether and the pooled extracts were dried over MgSO4. Flash chromatography (50 mm diameter column, 10% ethyl acetate in petroleum ether eluent, 2% H3PO4 in MeOH treated silica gel) afforded 3.41 g (9.18 mmol, 95%) of a light yellow solid which was recrystallized from 85:15 petroleum ether:benzene. This resulted in 1.98 g of a white powder which were dried at 84° C. for 31 hours followed by recrystallization from 85:15 petroleum ether:benzene once again. Drying at 84° C. for 24 hours resulted in 1.41 g of a white powder, m.p. 96°-97° C. The toluene was then removed in vacuo refluxed for 20 minutes under nitrogen extracted with 4×80 mL of 2.5N NaOH Drying (MgSO4) and flash chromatography (75 mm diameter column, 8% ethyl acetate in petroleum ether eluent)

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

Procedure: A solution of 1-ethyl-4-(5-hexenyl)-2-oxocyclohexaneacetic acid methyl ester isomer B (4.24 g, 15.14 mmol) and 2-ethylphenylhydrazine (2.27 g, 16.7 mmol) in 30.3 mL of toluene was refluxed under nitrogen for 22 hours with azeotropic removal of water. The toluene was then removed in vacuo and replaced with 10.8 mL of acetic acid. The solution was treated with borontrifluoride etherate (2.79 g, 19.7 mmol, 2.42 mL) and refluxed for 20 minutes under nitrogen. The reaction mixture was poured into 120 mL of water and extracted with 4×80 mL of 2.5N NaOH. Drying (MgSO4) and flash chromatography (75 mm diameter column, 8% ethyl acetate in petroleum ether eluent) afforded 3.72 g (9.73 mmol, 64%) of 1,8-diethyl-4-(5-hexenyl)-2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid methyl ester. Of this, 3.68 g (9.66 mmol) were refluxed in a solution of ethanol (30.9 mL) and 2.5N NaOH (7.7 mL) for 45 minutes under nitrogen. The ethanol was then removed in vacuo and the residue was suspended in 120 mL of 1N HCl. It was extracted with 4×40 mL of ether and the pooled extracts were dried over MgSO4. Flash chromatography (50 mm diameter column, 10% ethyl acetate in petroleum ether eluent, 2% H3PO4 in MeOH treated silica gel) afforded 3.41 g (9.18 mmol, 95%) of a light yellow solid which was recrystallized from 85:15 petroleum ether:benzene. This resulted in 1.98 g of a white powder which were dried at 84° C. for 31 hours followed by recrystallization from 85:15 petroleum ether:benzene once again. Drying at 84° C. for 24 hours resulted in 1.41 g of a white powder, m.p. 96°-97° C. The toluene was then removed in vacuo refluxed for 20 minutes under nitrogen extracted with 4×80 mL of 2.5N NaOH Drying (MgSO4) and flash chromatography (75 mm diameter column, 8% ethyl acetate in petroleum ether eluent)

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

Procedure: This material can be prepared from (1S)-1-ethyl-2-oxo-4-(phenylmethyl)cyclohexaneacetic acid methyl ester as described in Example 2, Step (b), for racemic material by substituting phenylhydrazine for 2-ethylphenylhydrazine.

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

Procedure: The title compound was prepared from 2-oxobicyclo[4.1.0]heptane-1-acetic acid ethyl ester by a Fisher indole reaction with 2-ethylphenylhydrazine followed by ester hydrolysis as described in Example 1, Step 6, m.p. 154°-156° C. (foams).

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

Procedure: The title compound was prepared from 2-oxobicyclo[4.1.0]heptane-1-acetic acid ethyl ester by a Fisher indole reaction with 2-ethylphenylhydrazine followed by ester hydrolysis as described in Example 1, Step 6, m.p. 154°-156° C. (foams).

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

Procedure: The title compound was prepared from 2-oxobicyclo[4.1.0]heptane-1-acetic acid ethyl ester by a Fisher indole reaction with 2-ethylphenylhydrazine followed by ester hydrolysis as described in Example 1, Step 6, m.p. 154°-156° C. (foams).

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

Procedure: The title compound was prepared from 2-oxobicyclo[4.1.0]heptane-1-acetic acid ethyl ester by a Fisher indole reaction with 2-ethylphenylhydrazine followed by ester hydrolysis as described in Example 1, Step 6, m.p. 154°-156° C. (foams).