A. 1-(tert-Butoxycarbonyl)indoline. A 1-L, two-necked, round-bottomed flask, equipped with a reflux condenser fitted with a calcium chloride-filled drying tube, a pressure-equalizing addition funnel, and a magnetic stirring bar, is charged with 113.5 g (0.52 mol) of di-tert-butyl dicarbonate (Note 1) and 200 mL of tetrahydrofuran. Through the dropping funnel, 59.6 g (0.50 mol) of indoline is added to the reaction mixture with stirring over 30 min which maintains a steady evolution of carbon dioxide(Note 2). The reaction mixture is stirred at room temperature for an additional 3 hr followed by removal of the solvent with a rotary evaporator. The residual liquid is distilled under reduced pressure to give 107.6–107.8 g of 1-(tert-butoxycarbonyl)indoline (98% yield) as a colorless oil, bp 83–84°C at 0.1 mm, which on standing solidifies, mp 42–45°C (Note 3).

B. 1-(tert-Butoxycarbonyl)-7-indolinecarboxaldehyde. An oven-dried, 2-L, three-necked, round-bottomed flask, equipped with an argon inlet, 200-mL pressure-equalizing dropping funnel fitted with a rubber septum, a low temperature thermometer, and a 4.5-cm egg-shaped magnetic stirring bar (Note 4), is flushed with argon and charged with 32.9 g (0.15 mol) of 1-(tert-butoxycarbonyl)indoline, 27.2 mL (0.18 mol) of N,N,N',N'-tetramethylethylenediamine (TMEDA) (Note 5), and 750 mL of anhydrous ether (Note 6). The dropping funnel is charged with 167 mL (0.18 mol) of a 1.08 M solution of sec-butyllithium in cyclohexane via syringe (Note 7). Under a positive pressure of argon, the flask is immersed in a dry ice-acetone bath. When the internal temperature has reached ca. −70°C, a white precipitate of the starting material appears. The solution of sec-butyllithium is added dropwise to this suspension with rapid stirring over 30 min while keeping the internal temperature below −70°C. The dropping funnel is rinsed with 10 mL of anhydrous ether. The light brown mixture is stirred for an additional 2 hr at −78°C, during which time the precipitate completely dissolves and the color of the reaction mixture becomes deep brown. After the 2 hr has elapsed, 17.0 mL (0.22 mol) of N,N-dimethylformamide (DMF) is added dropwise through the addition funnel over a 10-min period (Note 8). After stirring the resulting mixture for 30 min at −78°C, 50 mL of saturated aqueous ammonium chloride solution is added through the dropping funnel over 15 min, and the cooling bath is removed (Note 9). When the internal temperature of the reaction mixture has reached −50°C, 50 mL of water is added dropwise, whereupon the deep orange color becomes light yellow. The reaction mixture is allowed to warm to 0°C and then poured into a 2-L separatory funnel containing water (200 mL). After thorough mixing, the layers are separated, and the aqueous phase is extracted with two 200-mL portions of ether. The combined organic layers are washed twice with 200 mL of saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure on a rotary evaporator followed by exposure to oil pump vacuum to remove as much of the volatiles as possible. The residue is chromatographed on 750 g of silica gel (Note 10), using a carefully packed 8-cm diameter glass column, and a mixture of toluene and ethyl acetate (30:1) as the eluent (Note 11). The appropriate fractions are combined and concentrated to give crude 1-(tert-butoxycarbonyl)-7-indolinecarboxaldehyde (23.6–25.5 g, 64–69% yield) as a light yellow solid. Recrystallization of this solid from a mixture of ethyl acetate and hexane affords the pure aldehyde (20.5–21.1 g, 55–57% yield in two crops) as practically colorless needles, mp 86.5–87.5°C (Note 12).

C. 7-Indolinecarboxaldehyde. A 300-mL Erlenmeyer flask fitted with a magnetic stirring bar is charged with 150 mL of concentrated (36%) hydrochloric acid. To this magnetically stirred solution, 19.8 g (0.08 mol) of finely powdered 1-(tert-butoxycarbonyl)-7-indolinecarboxaldehyde is added portionwise over 15 min at room temperature. The starting material gradually dissolves accompanied by gas evolution. After 2 hr, the resulting orange-colored solution is poured into a 2-L beaker containing crushed ice (500 g). To this mixture, 120 mL of 28% aqueous ammonia solution is added slowly with stirring, and the resulting mixture containing a yellow precipitate is transferred to a 2-L separatory funnel and extracted with four 100-mL portions of dichloromethane. The combined extracts are washed with 100 mL of saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. The resulting yellowish brown oil is passed through 300 g of silica gel (Note 10) packed in an 8-cm diameter glass column using a mixture of toluene and ethyl acetate (30:1) as an eluent. The yellow eluates are combined, and the solvent is removed to give pure 7-indolinecarboxaldehyde (10.6–11.2 g, 90–95% yield) as a yellow solid, mp 48.5–49°C (Note 13).