Lithium Chloride → HCID 117642571, compound

Participants

Reaction Steps

lithium chloride complex (1.3 M in THF, 315 μL, 0.410 mmol) was added dropwise to a stirred solution of 3,4-bis(benzyloxy)-5-iodo-1-(4-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide (65) [prepared using the same procedure as Example S step (i) using (9) as starting material] (211 mg, 0.36 mmol) in THF (1.2 mL) at 0° C., the reaction mixture was allowed to stir for 15 min and isopropylmagnesium chloride. lithium chloride complex (1.3 M in THF, 100 μL, 0.13 mmol) was added, and the reaction mixture was allowed to stir for a further 15 min. A solution of dimethylphosphinic chloride (61 mg, 0.54 mmol) in THF (0.6 mL) was added and the reaction allowed to warm to RT and stirred for a further 16 h. The reaction mixture was quenched with 5% AcOH in MeOH (5 mL) and the volatiles removed in vacuo. The residue was purified by silica gel chromatography (12 g, 0-5% MeOH in DCM) to afford a crude residue. The crude residue was further purified by preparative HPLC (Waters, Acidic (0.1% Formic acid), Waters X-Select Prep-C18, 5 μm, 19×50 mm column, 30-60% MeCN in water) to afford 3,4-bis(benzyloxy)-5-(dimethylphosphoryl)-1-(4-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide (66) (29 mg, 15%) as a colourless gum: m/z 533 (M+H)+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 7.44-7.28 (m, 12H), 6.92-6.87 (m, 2H), 5.22 (s, 2H), 5.05 (s, 2H), 3.82 (s, 3H), 2.76 (s, 3H), 2.63 (s, 3H), 1.41 (br d, J=13 Hz, 6H).

Provenance & Evidence