4-Methylmorpholine → HCID 54318947, compound

Participants

Reaction Steps

To a suspension of triphenyl cyanomethyl phosphonium bromide (1, 0.68 g, 1.8 mmol) in anhydrous THF (10 mL) cooled in an ice bath was added triethylamine (396 mg, 546 μL, 3.9 mmol) and the mixture stirred in an ice bath for 15 min. To a solution of N-t-butyloxycarbonyl-β-benzylaspartic acid (2, 575 mg, 1.8 mmol) in THF (15 mL) cooled to -15° C. was added N-methyl morpholine (180 mg, 196 μL, 1.8 mmol) followed by iso-butylchloroformate (243 mg, 231 μL, 1.8 mmol). The resulting solution was stirred at -15° C. for 5 min before being added dropwise with stirring to the previously prepared cyanomethylphosphorane solution. The mixture was stirred at 0° C. for 15 min and then allowed to warm to room temperature and then stirred for a further 16 h. The precipitate was removed by filtration and the solvent removed under reduced pressure. The mixture was purified by chromatography on silica gel (0-50% ethyl acetate in hexane) to yield the product as a clear oil which solidified on drying (0.76 g, 70%): mp 42°-44° C.; 1H NMR (CDCl3) δ1.39 (s, 9H, Boc CH3 's), 2.99 (d, 2H, β--CH2), 5.06 (m, 3H, α--CH & benzyl CH2), 5.62 (d, 1H, NH), 7.28 (m, 5H, benzyl aromatic CH's), 7.52 (m, 15H, PPh3 aromatic CH's); MS (EI, calculated for C36 H35N2O5P, 606.2284) m/e 606.2292 (M+).

Provenance & Evidence