Hydrochloric Acid → (2S,3aR,7aS)-Octahydro-1H-indole-2-carboxylic acid hydrochloride

Participants

Reaction Conditions

Reaction Steps

In a 500 mL reaction flask equipped with a distillation head was added 33.5 g (0.143 mol, 1.0 equiv.) of (2S,3aR,7aS)-Ethyl octahydro-1H-indole-2-carboxylate hydrochloride (16), 102 g of water, and 102 g of conc. hydrochloric acid. The contents were heated to 94-96° C. temperature with mixing for NLT 6 h while collecting about 9 mL of distillate at atmospheric pressure. The reaction mixture was cooled to room temperature and concentrated to dryness on a rotary evaporator. To the resulting crude product, 255 mL of acetonitrile was added and heated for 1 h at reflux with mixing to break up and dissolve the solids. The mixture was cooled gradually to 0-5° C. temperature at a rate of 10-15° C. per h, and held at 0-5° C. for NLT 2 h under nitrogen atmosphere. The solids were collected via filtration and washed with 10-20 mL of chilled (0-5° C.) acetonitrile. The product was dried at 45° C. under vacuum for 16 h to afford 25.6 g of (2S,3aR,7aS)-Octahydro-1H-indole-2-carboxylic acid hydrochloride (5) in 86.9% yield as a white solid. 1H NMR (D2O, 400 MHz): δ 4.42 (dd, 1H, J=11.1, 2.7 Hz), 2.93, (dt, 1H, J=11.8, 3.6 Hz), 2.36 (ddd, 1H, J=12.9, 6.7, 2.7 Hz), 2.31-2.16 (m, 1H), 2.11-2.01 (m, 2H), 1.92-1.90 (m, 1H), 1.79-1.75 (m, 1H), 1.68-1.53 (m, 2H), 1.34-1.13 (m, 3H); LC-MS (m/z): 170.1 (M+H)+. The isolated product (5) correlates to the material prepared according to U.S. Pat. No. 487,932 and Tetrahedron Lett., 1992, 33, 4889.

Provenance & Evidence