Phosphorus oxychloride → 1,4-Difluoro-2-(isocyano(tosyl)methyl)benzene

Participants

Reaction Conditions

Reaction Steps

To a solution of N-((2,5-difluorophenyl)(tosyl)methyl)formamide (5.92 g, 18.2 mmol) in DME (100 mL) at about −10° C. was added phosphorus oxychloride (Fluka, 5.09 mL, 54.6 mmol) followed by dropwise addition of TEA (12.7 mL, 91.0 mmol) in DME (10 mL). The reaction mixture was stirred at about −5° C. for about 3 h. The reaction mixture was poured into ice-cold water (250 mL) and extracted with EtOAc (3×50 mL). The organic layer was dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography using heptane/EtOAc (gradient; 1:0 to 1:1) to give the title compound (1.90 g, 34.0%) as a yellow solid. LC/MS (Table 1, Method a) Rt=2.94 min; MS m/z: 306.1 (M−H)−.

Provenance & Evidence