Methyl iodide → HCID 10076103, compound

Participants

Reaction Steps

To a solution of N2-[(3,5-difluorophenyl)acetyl]-N1-[(2R,3R)-2-(3,5-difluorophenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl]-L-alaninamide (16) (85 mg, 0.16 mmol) in DMF (1 ml) was added a 60% suspension of NaH (6.6 mg, 0.165 mmol). The reaction was stirred at RT for 5 min and methyl iodide (23 mg, 0.16 mmol) was added via syringe. The reaction was stirred at RT for 3 h and was quenched with dropwise addition of 1N HCl, diluted with water and extracted with ethyl acetate. The organic phase was collected and washed with H2O, dried, filtered and evaporated to yield a crude oil (85 mg). The crude product was purified by flash chromatography (50% ethyl acetate/hexanes) to afford the title compound (17) (70 mg, 80%) as a 1:1 mixture with the 2S,3S diastereomer as a white solid. 1H NMR (300 MHz, CDCl3) δ0.99 (d, 1.5H), 1.17 (d, 1.5H), 3.44 (s, 1H), 3.46 (s, 1H), 3.50 (s, 3H), 4.24 (m, 1H), 4.70 (m, 1H), 5.15 (m, 1H), 5.77 (d, 0.5H), 5.91 (d, 0.5H), 6.46 (dd, 1H), 6.65-6.92 (m, 6H), 7.31 (m, 2H), 7.51 (m, 1H), 7.71 (m, 1H). MS APCI, m/z=546 (M+1). LC/MS: 2.80 min.

Provenance & Evidence