Dimethylformamide → Methyl (5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)methylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a flask under N2 charged with 2-(5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)acetic acid (1.033 g, 3.57 mmol) was added anhydrous CH2Cl2 (40 mL). The heterogeneous solution was cooled to 0° C. and oxalyl chloride (1.6 mL, 17.8 mmol) was added, followed by a catalytic amount of DMF. The solution was warmed to rt and maintained for 1 h. The solution was concentrated, then taken up in anhydrous acetone and added to a stirring aqueous solution of sodium azide (1.62 g, 25.0 mmol, in 10 mL H2O) at 0° C. to generate a homogeneous orange solution. After 15 min at 0° C., the mixture was diluted further with CH2Cl2 and stirred an additional 5 min to give a homogeneous solution. The solution was then partitioned between H2O and CH2Cl2, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×10 mL) and the combined organic layers were dried (Na2SO4) and concentrated in vacuo. The residue was transferred to a dry flask, evacuated and flushed with N2 (5×), and anhydrous CH2Cl2 (30 mL) was added. The solution was cooled to −78° C., and boron trichloride (5.4 mL, 5.4 mmol, 1.0 M in CH2Cl2) was added dropwise. The cold bath was removed and the solution was allowed to warm to rt, and maintained 48 h. Anhydrous methanol (5 mL) was added and the solution maintained at rt for 3 h at which time it was concentrated for purification by MPLC (Teledine Isco combiFlash Companion). The residue was taken up in minimal CH2Cl2 and absorbed onto a 25 g loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (80 g) using 99:1 CH2Cl2: MeOH to 90:10:1 CH2Cl2: MeOH:NH4OH to afford methyl (5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)methylcarbamate (680 mg, 60% yield) as a brown amorphous solid. LRMS (ESI) m/z calcd for C16H13F2N2O3 (M+H) 319.1. found 319.2.

Provenance & Evidence