ethyl 4-chloro-2-[(4-fluorophenyl)diazenyl]-3-oxobutanoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-fluoroaniline (10 g, 90.0 mmol, 1.0 eq.) in DCM/HOAc (1/1, 180 mL, 0.5M) at 0° C. was added dropwise a precooled solution of sodium nitrite (9.02 g, 108 mmol, 1.2 eq.) in conc. sulfuric acid (40 mL). After stirring for 30 min at 0° C. a mixture of ethyl 4-chloroacetoacetate (14.6 mL, 17.8 g, 108 mmol, 1.2 eq.) in HOAc (60 mL) and H2O (120 mL) was added within 5 min. After further 15 min at 0° C. a solution of sodium acetate (100 g, 1.219 mol, 13.5 eq.) in H2O (210 mL) was added slowly. The mixture was stirred for 30 min at 0° C. and 1 h at RT. DCM (200 mL) was added and the organic phase was separated. The aq. phase was extracted with DCM (3×100 mL). The combined organic phase was washed with water, phosphate buffer and subsequent with brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give the product ethyl 4-chloro-2-(4-fluorophenyl)azo-3-oxo-butanoate as a orange solid. MS (ES) C12H12ClFN2O3 requires: 286. Found: 287 (M+H)+ and 309 (M+Na)+. was added within 5 min The mixture was stirred for 30 min at 0° C. and 1 h at RT the organic phase was separated The aq. phase was extracted with DCM (3×100 mL) The combined organic phase was washed with water, phosphate buffer and subsequent with brine The organic layer was dried over Na2SO4 concentrated under reduced pressure