1-Bromo-2,4-difluorobenzene → HCID 68416544, compound

Participants

Reaction Conditions

Reaction Steps

2,4-Difluorobromobenzene (2 mmol), t-butyl 1,4-diazepane-1-carboxylate (3 mmol), Pd2(dba)3 (0.04 mmol, 4 mol % Pd, 36 mg), BINAP (0.08 mmol, 50 mg), potassium t-butoxide (KO-t-Bu, 2.8 mmol, 314 mg), and toluene (10 mL) are added to an oven-dried Schienk flask that is purged with argon for approximately 15 min. The reaction mixture is then heated to 90° C. under argon until all of 2.4-difluorobromobenzene is consumed as determined by GC analysis. The reaction mixture is then allowed to cool to RT, diluted with EtOAc (20 mL) and filtered through a Celite pad. The filtrate is evaporated, and purified by silica gel column chromatography to afford t-butyl 4-(2,4-difluorophenyl)-1,4-diazepane-1-carboxylate which is deprotected by TFA in DCM. The reaction mixture is concentrated and the residue is extracted twice with DCM to afford 1-(2,4-difluorophenyl)-1,4-diazepane as a yellow oil: LC/MS (M+1=213.31). 1H NMR (CDCl3, 400 MHz) δ 1.82 (br s, 1H, NH), 1.91 (quintuplet, 2H, J=6.0 Hz), 2.97 (t, 2H, J=5.6 Hz), 3.05 (t, 2H, J=5.2 Hz), 3.33 (m, 4H), 6.70-6.87 (m, 3H).

Provenance & Evidence