2,3-dihydro-1H-indene-2-carbonitrile

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

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methanesulfonic acid indan-2-yl ester (18.65 g, 87.9 mmol) and tetraethylammonium cyanide (15.10 g) in acetonitrile (180 mL) was heated to 55° C. for 5 hours, cooled and concentrated. The residue was partitioned between ethyl acetate and water, and the organic phase separated. This was dried over MgSO4 and the filtered solution was concentrated and then separated by column chromatography (dichloromethane:ethyl acetate, 6:1-1:1) to give the product as a red solid (6.51 g, 52%). cooled concentrated The residue was partitioned between ethyl acetate and water the organic phase separated This was dried over MgSO4 the filtered solution was concentrated separated by column chromatography (dichloromethane:ethyl acetate, 6:1-1:1)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methanesulfonic acid indan-2-yl ester (18.65 g, 87.9 mmol) and tetraethylammonium cyanide (15.10 g) in acetonitrile (180 mL) was heated to 55° C. for 5 hours, cooled and concentrated. The residue was partitioned between ethyl acetate and water, and the organic phase separated. This was dried over MgSO4 and the filtered solution was concentrated and then separated by column chromatography (dichloromethane:ethyl acetate, 6:1-1:1) to give the product as a red solid (6.51 g, 52%). cooled concentrated The residue was partitioned between ethyl acetate and water the organic phase separated This was dried over MgSO4 the filtered solution was concentrated separated by column chromatography (dichloromethane:ethyl acetate, 6:1-1:1)

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

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

Procedure: 4-|cis-2,6-Dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl|-indan-2-carbonitrile. Triethylamine (200 μL, 1.4349 mmol) and phosphorus oxychloride (74 μL, 0.7939 mmol) were added to a solution of 4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid amide (254 mg, 0.5105 mmol) in dichloroethane (3 mL). The reaction was stirred for 4 h at room temperature then directly purified by silica gel column chromatography (0-50% EtOAc in hexanes) to afford 4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carbonitrile (23 mg, 9%). 1H NMR (400 MHz, CD3OD) δ ppm 7.77 (d, 1H), 7.54 (d, 1H), 7.42 (t, 1H), 7.10 (d, 2H), 6.93 (d, 2H), 4.20-4.00 (m, 2H), 3.65-3.60 (m, 1H), 3.60-3.40 (m, 2H), 3.40-3.20 (m, 4H), 2.80-2.60 (m, 2H), 1.50 (d, 6H). LCMS: 480.0 (M+1)+. then directly purified by silica gel column chromatography (0-50% EtOAc in hexanes)

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

Procedure: Fuming nitric acid (40 ml, 1.5 g/ml) was added dropwise with stirring to acetic anhydride (80 ml ) keeping the temperature of the mixture at 0° C. After the addition was complete 2-cyanoindane (11.33 g, 79.5 mmol), (J. Chem. Soc. (B), (1969), 1197) was added dropwise with stirring over 30 minutes maintaining the reaction temperature between -5° and 0° C. The mixture was stirred for a further 15 minutes then poured onto ice. The mixture was extracted with dichloromethane (4×150 ml) and the extracts were washed with saturated aqueous sodium bicarbonate (3×150 ml), dried over magnesium sulphate and the solvent evaporated under reduced pressure. The residue was recrystallised from ethanol to give 2-cyano-5-nitroindane (12.09 g, 81%) as a yellow solid, m.p. 80°-82° C. at 0° C After the addition was added dropwise maintaining the reaction temperature between -5° and 0° C The mixture was stirred for a further 15 minutes then poured onto ice The mixture was extracted with dichloromethane (4×150 ml) the extracts were washed with saturated aqueous sodium bicarbonate (3×150 ml) dried over magnesium sulphate the solvent evaporated under reduced pressure The residue was recrystallised from ethanol

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methanesulfonic acid indan-2-yl ester (18.65 g, 87.9 mmol) and tetraethylammonium cyanide (15.10 g) in acetonitrile (180 mL) was heated to 55° C. for 5 hours, cooled and concentrated. The residue was partitioned between ethyl acetate and water, and the organic phase separated. This was dried over MgSO4 and the filtered solution was concentrated and then separated by column chromatography (dichloromethane:ethyl acetate, 6:1-1:1) to give the product as a red solid (6.51 g, 52%). cooled concentrated The residue was partitioned between ethyl acetate and water the organic phase separated This was dried over MgSO4 the filtered solution was concentrated separated by column chromatography (dichloromethane:ethyl acetate, 6:1-1:1)