(1S,2S)-2-(N-Tosylamino)cyclohexanecarboxylic acid (CAS NO.: 110456-11-6)could be produced through the following synthetic routes.

A. (5aS,9aS,11aS)-Perhydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione (CAS NO.: 110419-86-8) (1). A 3-L, three-necked, round-bottomed flask, equipped with a mechanical stirrer bearing a glass paddle, a dry ice/acetone-cooled cold-finger condenser bearing a nitrogen inlet/outlet valve vented through a mineral oil bubbler, and a gas inlet is placed under a nitrogen atmosphere, and charged with 25.0 g (0.116 mol) of 99% pure (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)dione and a solution of 42.2 g (0.570 mol) of tert-butyl alcohol in 150 mL of dry tetrahydrofuran (THF). The mixture is cooled to -78°C (dry ice/acetone bath) and 2 L of dry ammonia is distilled into the mixture. After stirring is initiated, a total of 35.7 g (0.912 mol) of potassium metal is added to the reaction mixture in small chunks at -78°C, and the resulting blue-colored solution is stirred for 1 hr. The reaction is then carefully quenched at -78°C by the addition of 61 g (1.14 mol) of solid ammonium chloride. The cooling bath and condenser are removed, and the ammonia is allowed to evaporate overnight. The residue is suction filtered, and the filter cake is washed with 100 mL of chloroform. The filtrate is diluted with 200 mL of water, transferred to a 1-L separatory funnel, the organic phase is separated, and the aqueous phase is extracted three times with 100 mL of chloroform. The combined organic layers are dried over anhydrous sodium sulfate (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue is crystallized from ethyl acetate, and the mother liquor purified by chromatography to give a total of 17.8 g (69%) of 1 (R_f 0.31, EtOAc/MeOH, 9:1) as a colorless solid, mp 225–227°C, [α]_D23 +55° (CHCl₃, c 0.61).

B. (1S,2S)-2-Amino-1-[((2S)-2-carbomethoxypyrrolidinyl)carbonyl]cyclohexane (CAS NO.: 174624-00-1) (2). A 250-mL, single-necked, round-bottomed flask equipped with a condenser bearing a nitrogen inlet/outlet valve as above (Part A) and a magnetic stirring bar, is charged with a solution of 20.0 g (90.0 mmol) of 1, 100 mL of anhydrous methanol, and 18.4 g (180 mmol) of concentrated sulfuric acid, placed under a nitrogen atmosphere, and heated at reflux (oil bath temperature at 80–85°C) for 48 hr or until TLC analysis indicates the disappearance of 1. The solution is concd under reduced pressure, 100 mL of dichloromethane (CH₂Cl₂) is added, and the mixture is cooled to 0°C. A total of 150 mL of saturated aqueous sodium bicarbonate solution is added in small portions with good stirring, followed by 10–12 mL of concd ammonium hydroxide until a pH of 10 is reached. After thorough mixing, the organic phase is separated and the aqueous phase is extracted twice with 50 mL of CH₂Cl₂. The combined organic phases are dried over Na₂SO₄, concentrated, and the resulting crude amine 2 used immediately in the next step.

C. (1S,2S)-2-(N-Tosylamino)-1-[((2S)-2-carbomethoxypyrrolidinyl)carbonyl] cyclohexane (CAS NO.: 110419-91-5)(3). Approximately 22.9 g (90 mmol) of crude amine 2 (prepared above in part B), 13.66 g (135 mmol) of triethylamine, and 100 mL of dry THF are placed in a 300-mL, round-bottomed flask, equipped with a pressure-equalizing dropping funnel, a magnetic stirring bar, and a nitrogen inlet. The dropping funnel is charged with a solution of 18.9 g (99.1 mmol) of p-toluenesulfonyl chloride in 50 mL dry THF. The reaction mixture is cooled to 0°C with magnetic stirring, and the solution of p-toluenesulfonyl chloride is delivered dropwise over a 30-min period. The resulting cloudy solution is stirred for 60 hr at ambient temperature. After this time period, the reaction mixture is diluted with 50 mL of saturated sodium chloride solution and 50 mL of ethyl acetate, transferred to a 500-mL separatory funnel, mixed thoroughly, and the organic phase separated. The aqueous phase is extracted twice with 50 mL of ethyl acetate. The combined organic layers are dried (Na₂SO₄), filtered, concentrated under reduced pressure, and the resulting residue purified by chromatography to give 22.43 g (61% from 1) of 3 (R_f 0.34, CHCl₃/EtOAc, 1:1) as a colorless solid, mp 144–146°C.

D. (1S,2S)-2-(N-Tosylamino)cyclohexanecarboxylic acid (CAS NO.: 110456-11-6)(4). A 250-mL round-bottomed flask, equipped with a water-cooled condenser, is charged with 28.8 g (70.5 mmol) of 3 and 120 mL of 6 M sulfuric acid. The resulting heterogeneous mixture is heated at reflux (oil bath temperature 110–115°C) for 14 hr. After several hours at reflux, suspended solids are observed. The mixture is cooled to room temperature, transferred to a 500-mL separatory funnel, and extracted three times with 100 mL of CH₂Cl₂. The combined organic layers are dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford 4 as a colorless solid. Recrystallization of the crude solid 4 from CH₂Cl₂ and ethyl acetate affords 12.16 g (58%) of pure 4(R_f 0.29, CHCl₃/EtOAc, 1:1) as colorless needles, mp 175–177°C, [α]_D20 +35° (CHCl₃, c 0.50).