Allyl bromide → N-(3-(allyloxy)-1-(3-methoxyphenyl)propyl)-2,2,2-trifluoroacetamide

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Reaction Steps

Step R (2): 2,2,2-Trifluoro-N-(3-hydroxy-1-(3-methoxyphenyl)propyl)acetamide from step R (1) (1.99 g, 7.18 mmol) was dissolved in THF (20 mL) and chilled to −78° C. n-BuLi (5.76 mL, 14.4 mmol, 2.5 M in hexanes) and DMPU (1.73 mL, 14.4 mmol) were added and the resulting mixture was stirred for 45 min. Allyl bromide (3.04 mL, 36 mmol) was added. The mixture was warmed to rt and then heated to reflux for 3 days. The mixture was quenched with saturated NH4Cl. After 15 min, the mixture was diluted with 1 N NaOH and the aqueous mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by silica-gel column chromatography (0%-25% EtOAc/Hexanes) afforded 610 mg (27% yield) of N-(3-(allyloxy)-1-(3-methoxyphenyl)propyl)-2,2,2-trifluoroacetamide as a viscous yellow oil. LC-MS (M+H)+=318.37; 1H NMR (300 MHz, CDCl3) δ ppm 1.89-2.01 (m, 1H) 2.14-2.29 (m, 1H) 3.34-3.52 (m, 2H) 3.77 (s, 3H) 3.91 (d, J=5.86 Hz, 2H) 5.10-5.30 (m, 3H) 5.79-5.95 (m, 1H) 6.70-6.82 (m, 3H) 7.19-7.29 (m, 1H).

Provenance & Evidence