1-(2-amino-6-chlorophenyl)ethanone

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At a temperature of 65° C., sodium borohydride was added to a solution of 1-(2-amino-6-chloro-phenyl)-ethanone in ethanol, and the mixture was heated overnight (65° C.). Water, KSCN and HCl were then added subsequently, and the mixture was again heated (3 h, 65° C.). The majority of the title compound precipitated upon cooling and could be isolated in sufficiently pure form by filtration. A small additional amount of the desired product was obtained by workup of the mother liquor (evaporation of solvent, column chromatography [silica gel, solvent gradient n-heptan/ethyl acetate=100/0−60/40]). The title compound was obtained in a combined yield of 1.46 g (43%). the mixture was again heated (3 h, 65° C.) The majority of the title compound precipitated upon cooling could be isolated in sufficiently pure form by filtration

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

Procedure: A suspension of 2-amino-6-chlorobenzonitrile (3.67 g, 24 mmol) in diethyl ether (60 ml) was added slowly to methylmagnesium bromide (56 ml, 3 M in Et2O, 170 mmol), and the mixture was heated to reflux, until all starting material was consumed (3 h, HPLC control). The mixture was then placed in an ice bath, and HCl (6M, 58 ml) was slowly added (vigorous reaction). The mixture was then again heated to reflux, cooled and made alkaline by addition of solid Na2CO3. The mixture was extracted several times with ethyl acetate, the combined organic phases were dried (Na2SO4), and the solvent was evaporated under reduced pressure. Purification of the residue by column chromatography (silica gel, solvent gradient n-heptan/ethyl acetate=100/0−60/40) gave the title compound (2.72 g, 67%). 1H NMR (CDCl3): δ 2.65 (3H, s), 4.91 (2H, bs), 6.58 (1H, d), 6.73 (1H, d), 7.07 (1H, t). the mixture was heated to reflux, until all starting material was consumed (3 h, HPLC control) The mixture was then placed in an ice bath HCl (6M, 58 ml) was slowly added (vigorous reaction) The mixture was then again heated to reflux cooled The mixture was extracted several times with ethyl acetate the combined organic phases were dried (Na2SO4) the solvent was evaporated under reduced pressure Purification of the residue by column chromatography (silica gel, solvent gradient n-heptan/ethyl acetate=100/0−60/40)