Dimethylformamide → HCID 58041276, compound

Participants

Reaction Conditions

Reaction Steps

5-Chloro-2-fluorobenzotrifluoride (1.5 g, 7.5 mmol) was dissolved in dry tetrahydrofuran (THF; 10 mL), treated with tetramethylethylenediamine (TMEDA; 1.6 mL, 1.2 g, 11 mmol), cooled to −78° C. and treated in portions with n-butyl lithium (n-BuLi, 2.5 M in hexanes; 3.9 mL, 9.8 mmol). After stirring at −78° C. for 90 minutes (min), the mixture was treated with N,N-dimethylformamide (DMF; 770 microliters (μL), 730 mg, 10 mmol) and stirred for a further 30 min. The cooling bath was removed and mixture warmed to 25° C. over 30 min. The reaction was quenched by addition of satd ammonium chloride (NH4Cl) solution then diluted with diethyl ether (Et2O; 30 mL). The separated organic phase was washed with satd NaCl (10 mL), dried (Na2SO4) and evaporated. The residue was dissolved in dry methanol (CH3OH; 10 mL) and treated with 30% sodium methoxide solution in CH3OH (14 g). The mixture was stirred at 25° C. for 20 h, diluted with H2O (50 mL) and extracted with Et2O (2×40 mL). The combined organic phases were washed with satd NaCl solution (20 mL), dried (Na2SO4) and evaporated. The residue was purified by silica gel chromatography using a 0 to 10% EtOAc gradient in hexane to give the benzaldehyde (1.1 g). This material (1.0 g, 4.2 mmol) was dissolved in dry CH2Cl2 (10 mL), cooled to −78° C. and treated with BBr3 (1 M solution in CH2Cl2; 5 mL, 5 mmol). The mixture was allowed to warm to 25° C. and stirred for 22 h. After cooling to −45° C., the mixture was treated with H2O (5 mL), warmed to 25° C. and extracted with EtOAc (2×15 mL). The combined extracts were washed with satd NaCl solution (10 mL), dried (Na2SO4) and evaporated. The residue was purified by silica gel chromatography using a 0 to 10% EtOAc gradient in hexane to give the aldehyde (950 mg): 1H NMR (400 MHz, CDCl3) δ 11.61 (s, 1H), 9.91 (s, 1H), 7.79 (d, J=2.5 Hz, 1H), 7.75 (d, J=2.6 Hz, 1H); EIMS m/z 224.

Provenance & Evidence