Methyl iodide → HCID 59468908, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate (D66, 480 mg, 1.04 mmol) and methyl iodide (130 μl, 2 mmol) in dry DMF (5 ml) at 0° C. was added sodium hydride (60 mg, 1.5 mmol, 60% dispersion in mineral oil) and the mixture was stirred for 1.5 h from 0° C. to r.t. A second batch of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate (D62, 46 mg, 0.1 mmol) was dissolved in dry DMF (0.5 ml) and methyl iodide was added. The mixture was cooled at 0° C. and sodium hydride (6 mg, 0.15 mmol, 60% dispersion in mineral oil) was added and the mixture was stirred for 1.5 h from 0° C. to r.t. The reactions were quenched with brine/ice and the two mixtures were combined and extracted with ethyl acetate. The organic layer was washed three times with ice cold brine, dried (Na2SO4) and evaporated to afford the title compound as a colourless oil (540 mg); Rt (HPLC): 6.89 min; MS: (ES/+) m/z: 496 [M+Na] C26H32FNO6 requires 473; 1H NMR (400 MHz, CDCl3) δ(ppm): 7.48-7.59 (m, 1H); 7.42-7.48 (m, 2H); 7.28-7.36 (m, 1H); 7.13-7.21 (m, 1H); 7.03-7.13 (m, 1H); 6.89-7.00 (m, 2H); 5.13 and 5.16 (s, s, 2H); 4.94-5.06 and 4.74-4.83 (m, m, 1H); 4.09-4.19 (m, 1H); 3.78-3.96 (m, 1H); 3.83 (s, 3H); 3.41 (s, 3H); 2.44-2.70 (m, 1H); 2.17-2.36 (m, 2H); 1.69-1.87 (m, 1H); 1.11 and 1.40 (s, s, 9H).

Provenance & Evidence