Methyl iodide → [1-(3-Chloro-4-cyano-2-methylphenyl)-3-methyl-2,5-dioxoimidazolidin-4-ylmethyl]carbamic Acid tert-butyl Ester

Participants

Reaction Steps

To a solution of the hydantoin 13A (1.00 g, 2.64 mmol) in DMF (10 mL) was added KHMDS (530 mg, 2.64 mmol) followed by iodomethane (0.16 mL, 2.64 mmol) and the resulting solution was stirred at rt for 2 h. The solution was then diluted with water and extracted with EtOAc. The organic layer was washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, CH2Cl2/CH3OH, 100:0 to 80:20 gradient) to afford the title compound (608 mg) as a white foam. 1H NMR (CDCl3) δ 1.41, 1.43 (s, 9H), 2.26, 2.28 (s, 3H), 3.11, 3.12 (s, 3H), 3.60-3.86 (m, 2H), 4.08-4.12 (m, 1H), 4.77, 4.83 (br s, 1H), 7.16, 7.20 (d, J=8.3 Hz, 1H), 7.60, 7.61 (d, J=8.3 Hz, 1H); HPLC a) column: Phenominex C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold, 4 mL/min, UV detection at 220 nm, 3.05 min retention time; HPLC b) column: Shimadzu Shim-Pack VP-ODS C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold, 4 mL/min, UV detection at 220 nm, 2.86, 2.96 min retention time (98%); HPLC c) column: Daicel Chiralcel OD 4.6×250 mm, Isocratic 25% isopropanol/hexanes, 30 min, 1 mL/min, UV detection at 220 nm, 14.40 min retention time (97%); MS (ES) m/z 391 [M−H]−.

Provenance & Evidence