(2S)-(-)-3-(-)-exo-(Dimethylamino)isoborneol (CAS NO.: 103729-96-0), which is known as Bicyclo[2.2.1]heptan-2-ol, 3-(dimethylamino)-1,7,7-trimethyl-, [1R-(exo,exo)]-, could be produced through the following synthetic routes.

A. (2S)-(-)-3-exo-Aminoisoborneol (CAS NO.: ), 2. All glassware for this step must be oven-dried prior to use. A 2-L, three-necked, round-bottomed flaskequipped with an efficient mechanical stirrer attached to a stirring blade, a thermometer, and a 1-L pressure-equalizing addition funnel connected to an argon inlet is flushed with argon and charged with 475 mL of dry diethyl ether and 5.12 g (0.14 mol) of lithium aluminum hydride. The addition funnel is charged with a solution of 8.46 g (0.047 mol) of (1R,4S)-(-)-camphorquinone monoxime (1) in 350 mL of dry ether. The reaction mixture is cooled to 0°C in an ice-water bath with stirring, and the solution of 1 is added slowly to the reaction mixture over 30 min. After the addition is complete, the addition funnel is replaced with a reflux condenser connected to the argon inlet, and the reaction flask is removed from the cooling bath. The reaction mixture is stirred and heated at reflux for 1.5 hr and then cooled to 0°C in an ice-water bath. The reaction is quenched very carefully by dropwise addition of 75 mL of saturated aqueous sodium sulfate solution. The resulting white granular precipitate or slurry is removed by vacuum filtration through Celite, and the filter cake is washed with three portions of 75 mL of chloroform . The combined filtrate and washings are dried over sodium sulfate , filtered, and concentrated by rotary evaporation at 40°C to give 8.07 g of crude (2S)-(-)-3-exo-aminoisoborneol (2) as an off-white solid. This material is suitable for the next reaction without purification.

B. (1R,2S,6R,7S)-1,10,10-Trimethyl-4-oxo-5-aza-3-oxatricyclo[5.2.1.0]decane (CAS NO.: 131897-87-5), 3. A 500-mL, single-necked, round-bottomed flask equipped with a 250-mL pressure-equalizing dropping funnel and a magnetic stirring bar is charged with 8.06 g (0.048 mmol) of crude (2S)-(-)-3-exo-aminoisoborneol (2), 70 mL of toluene , and 55 mL (0.12 mol) of 12.5% aqueous potassium hydroxide solution. The reaction flask is cooled to 0°C in an ice-water bath, the dropping funnel is charged with a solution of 50 mL (0.095 mol) of triphosgene (1.9 M in toluene ), and the triphosgene solution is slowly added over 40 min with vigorous stirring to the two-phase reaction mixture. After the reaction is complete, the reaction mixture is stirred at 0°C for 1 hr and diluted with 130 mL of ethyl acetate . The mixture is transferred to a 1-L separatory funnel, and the layers are separated. The organic layer is washed successively with 150 mL of saturated aqueous sodium bicarbonate solution and 150 mL of saturated sodium chloride solution. The organic layer is dried over magnesium sulfate , filtered, and concentrated by rotary evaporation to give 8.07 g of crude (1R,2S,6R,7S)-1,10,10-trimethyl-4-oxo-5-aza-3-oxatricyclo[5.2.1.0]decane (3) as a waxy pale yellow solid that is suitable for further reaction without purification.

C. N-Methyl-(1R,2S,6R,7S)-1,10,10-trimethyl-4-oxo-5-aza-3-oxatricyclo[5.2.1.0]decane , 4. All glassware for this step must be oven-dried. A 500-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar, an argon inlet, a 125-mL pressure-equalizing addition funnel, and a rubber septum is flushed with argon and charged with 9.47 g (0.083 mol) of a 35% dispersion of potassium hydride (KH) in mineral oil. The mineral oil is removed by introducing 85 mL of hexane with a syringe, gently stirring the mixture, allowing the potassium hydride to settle, and then withdrawing the liquid by syringe. The KH is washed twice using this procedure. The flask is further charged with 300 mL of dry tetrahydrofuran (THF)), and the dropping funnel is charged by syringe with a solution of 8.06 g (0.041 mol) of crude (1R,2S,3R,4S)-3-exo-amino-2-exo-hydroxy-1,7,7-trimethylbicyclo[2.2.1]heptane (3) in 90 mL of dry THF. The magnetically stirred suspension of potassium hydride is cooled to 0°C, and the solution of 3 is added dropwise over a 10-min period. After the addition is complete, the mixture is stirred at 0°C for 20 min, and 13 mL (0.21 mol) of methyl iodide is introduced dropwise via syringe. The cooling bath is removed, and the reaction mixture is stirred at room temperature for 10 hr. The reaction is quenched by cautious addition of 15 mL of water, and the resulting mixture is transferred to a 1-L separatory funnel containing 125 mL of water. The layers are separated, and the aqueous layer is extracted three times with 100 mL of ethyl acetate . The combined organic extracts are washed with 300 mL of saturated sodium chloride solution, dried over magnesium sulfate , and concentrated by rotary evaporation to give crude 4. Recrystallization of this material from 15 mL of cyclohexane provides brown crystals, which are dissolved in 15 mL ethyl acetate and decolorized with Norit SA3 (100 mesh) activated carbonat reflux. This solution is cooled to room temperature, and the Norit is removed by vacuum filtration through Celite. The filtrate is concentrated by rotary evaporation, and the resulting pale yellow crystals are recrystallized twice from 5 mL of cyclohexane to provide 2.77 g (32%) of N-methyl-(1R,2S,6R,7S)-1,10,10-trimethyl-4-oxo-5-aza-3-oxatricyclo[5.2.1.0]decane (4) as colorless crystals, mp 124-125°C, [α]_D ²² −39.6° (CH₂Cl₂, c 0.62).

D. (2S)-(-)-3-(-)-exo-(Dimethylamino)isoborneol, [(-)-DAIB] (CAS NO.: 103729-96-0), 5. Caution! Since DAIB slowly decomposes in air , samples of DAIB should be stored under nitrogen or argon . All glassware for this step must be oven-dried. A 250-mL, three-necked, round-bottomed flask equipped with a reflux condenser connected to an argon inlet, a magnetic stirring bar, a rubber septum, and a Teflon stopper, is flushed with argon and charged with 55 mL of dry THF and 5.20 g (0.075 mol) of lithium aluminum hydride. The solution is cooled to 0°C in an ice-water bath, and a solution of 2.77 g (0.013 mol) of N-methyl-(1R,2S,6R,7S)-1,10,10-trimethyl-4-oxo-5-aza-3-oxatricyclo[5.2.1.0]decane (4) in 35 mL of dry THF is introduced slowly with a cannula. After addition is complete, the flask is removed from the cooling bath, and the reaction mixture is heated at reflux for 18 hr. The reaction flask is cooled to 0°C in an ice-water bath, and the mixture is quenched by successive addition of 20 mL of ethyl acetate and 17 mL of saturated aqueous sodium sulfate solution. The white mixture is stirred at room temperature for 2 hr, and the resulting white granular precipitate or slurry is removed by vacuum filtration through Celite. The filter cake is washed with three 100-mL portions of ethyl acetate , and the combined filtrates are thoroughly dried over sodium sulfate , filtered, and concentrated by rotary evaporation to furnish crude 5 as an oil. Crude 5 is purified by bulb-to-bulb distillation to give 2.19 g (84%) of (2S)-(-)-3-exo-(dimethylamino)isoborneol, [(2S)-(-)-DAIB] (5) as a nearly colorless oil, bp 150°C (25 mm), [α]_D ²² 36° (ethanol, c 4.65).