Methanesulfonyl chloride → 2,3-Dihydro-1h-inden-2-yl methanesulfonate

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Reaction Conditions

Reaction Steps

N,N-Dimethyl-2-indanamine (107). Methanesulfonyl chloride (11.5 mL, 149 mmol) was added dropwise to a stirred solution of 2-indanol (106) (20 g, 149 mmol) and iPr2NEt (28.6 mL, 164 mmol) in DCM (300 mL) at 0° C., and the solution stirred at 20° C. for 16 h. The solution was washed with 1 M HCl (80 mL), aqueous saturated NaHCO3 solution (80 mL) and brine (100 mL), dried and the solvent evaporated. The residue was recrystallised from EtOH to give 2,3-dihydro-1H-inden-2-yl methanesulfonate (31.14 g, 98%) as a white solid. Aqueous HNMe2 (40%, 180 mL, 1.42 mol) was added slowly to a stirred solution of mesylate (30.25 g, 143 mmol) in DMF (200 mL) and the solution stirred at 20° C. for 16 h. The solution was partitioned between EtOAc (400 mL) and water (800 mL) and the organic fraction washed with water (3×80 mL), brine (100 mL), dried and the solvent evaporated. The residue was suspended in 1 M HCl (400 mL) and washed with DCM (3×80 mL). The pH of the aqueous fraction was adjusted to 14 with NaOH, the mixture chilled at 5° C. for 8 h and the precipitate filtered. The precipitate was washed with water (50 mL) and dried to give amine 107 (21.54 g, 93%) as a light gray solid: 1H NMR δ 7.10-7.17 (m, 4H, Harom), 3.01-3.08 (m, 3H, H-2, CH2), 2.82-2.91 (m, 2H, CH2), 2.31 [s, 6H, N(CH3)2].

Provenance & Evidence