Potassium tert-butoxide → HCID 178484151, compound

Participants

Reaction Steps

A solution of Intermediate 25, 2,5-Dichloro-4-pyrrolidin-1-ylmethyl-phenol (1.8 g, 7.5 mmol) and potassium tert-butoxide (0.85 g, 7.5 mmol) in DMSO (20 mL) was heated to 100° C. under vigorous stirring in a flow of argon. The mixture was stirred at this temperature for 15 min. A solution of intermediate 6, cis-3-{[(tert-butoxycarbonyl)(methyl)amino]methyl}cyclobutyl methanesulfonate (1.1 g, 3.8 mmol) in DMSO (10 mL) and tetrabutylammonium bromide (0.36 g, 1.14 mmol) were added. The mixture was stirred at 100° C. for 1 h, cooled, and diluted with Et2O (50 mL). The solution was washed with water (50 mL), 1N NaOH (3×25 mL), brine, dried with Na2SO4, and evaporated. The residue was purified by chromatography (silica gel 63-100μ, 20 mL, hexane/CHCl3 (20:80→0:100), then CHCl3/MeOH 100:0→80:20). The product containing fractions were collected and concentrated to give the title compound (0.93 g, 55%) as a yellow oil. 1H NMR-data (DMSO-d6): 7.49 (s, 1H, Ar—H); 6.95 (s, 1H); 4.85-5.00 (m, 1H); 3.60 (br.s, 2H); 3.35 (d, 2H, J=8. Hz); 2.78 (s, 3H, NCH3); 2.52-2.62 (m, 1H); 2.41-2.53 (m, 4H+DMSO); 2.22-2.30 (m, 2H); 2.08-2.20 (m, 2H); 1.65-1.74 (m, 4H); 1.43 (s, 9H, Boc).

Provenance & Evidence