Ethanol → HCID 71270610, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of 2-[(1R,2S)-5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-yl]-1H-isoindole-1,3(2H)-dione (7) (25.8 g, 0.0787 mol) in ethanol (260 mL, 4.4 mol) was added hydrazine (4.94 mL, 0.157 mol), and the flask was affixed with a reflux condenser and heated to a bath temperature of 90° C. A precipitate began to form after several minutes of stirring and after 1 hour of heating the mixture had become a thick slurry/solid. The reaction was cooled to room temperature and the solid reaction byproducts were filtered and washed with CH2Cl2 (˜300 mL). The volatiles were removed from the filtrate in vacuo, and the residue was suspended in CH2Cl2 (250 mL), at which point the solid byproducts were again removed by filtration. The volatiles were removed in vacuo, and the residue was again suspended in CH2Cl2 (˜50 mL). The solid byproducts were removed a final time by filtration to afford (1R,2S)-5-chloro-2-methoxyindan-1-amine (15.5 g, 99%) as a red/orange waxy solid. LCMS: (FA) ES+ molecular ion 198, major ionization 181; 1H NMR (400 MHz, DMSO) δ 7.30 (d, J=7.9, 1H), 7.25-7.16 (m, 2H), 4.14 (d, J=4.9, 1H), 3.89 (td, J=2.8, 4.9, 1H), 3.29 (s, 3H), 2.89 (ddd, J=3.8, 16.4, 21.3, 2H), 2.04 (s, 2H). Chiral HPLC (Chiralpak AD 4.6×250 column eluted with 95/5/0.1% hexane/EtOH/DEA @ 1.0 ml/min-30 min run) showed an ee of >99%.

Provenance & Evidence