Methyl iodide → HCID 69058266, compound

Participants

Reaction Steps

To a suspension of sodium hydride (8 mg of 60% dispersion in mineral oil, hexane-washed, 0.20 mmol) in 2 mL of THF was added (3aR,9bS)-tert-butyl 4-(2-hydroxyethyl)-5-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]isoquinoline-2(9bH)-carboxylate from Example 20, Part A (40 mg, 0.10 mmol) in 2 mL THF. The reaction was stirred for 20 min, at which time gas evolution had ceased. Then there was added iodomethane (0.125 mL of a 2M solution in tert-butyl methyl ether, 0.25 mmol) and the reaction was allowed to stir at ambient temperature for 18 h. TLC analysis showed that starting material remained. Additional sodium hydride (8 mg of 60% dispersion in mineral oil, 0.20 mmol) and iodomethane (0.125 mL of a 2M solution in tert-butyl methyl ether, 0.25 mmol) were added and the reaction was allowed to stir at 40° C. for 2 h. The reaction was quenched with 10 mL of 1N HCl and extracted with EtOAc. The organics were washed with sat'd aq NaHCO3 and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (230-400 mesh silica gel, elution with 4:1 hexane/EtOAc) to afford 15 mg (37%) of the title compound. 1H NMR (CDCl3): δ 7.79 (d, 1H, J=7.7 Hz), 7.57-7.52 (m, 2H), 7.25-7.22 (m, 1H), 4.15-4.10 (m, 1H), 4.08-3.98 (m, 2H), 3.82-3.77 (m, 1H), 3.61-3.54 (m, 2H), 3.50-3.27 (overlapping m, 4H), 3.31 and 3.28 (singlets, 3H), 1.50 (s, 9H).

Provenance & Evidence