Acetamide → Linezolid

Participants

Reaction Steps

Fluorination of 4-chloronitrobenzene with fluorine gas in sulfuric acid provided 4-chloro-3-fluoronitrobenzene as a crystalline solid on aqueous workup of the reaction. This was followed by displacement of the chloro group with morpholine (neat) in quantative yield, isolated as a crystalline solid on dilution of the reaction with methanol. Reduction of the nitro group with ammonium formate under an argon or nitrogen atmosphere provided 3-fluoro-4-morpholinoaniline as a crystalline solid which was converted to the isocyanate and treated with the chiral epoxide (S)N-(oxiranylmethyl)acetamide in xylene with lithium bromide and tributylphosphine oxide to yield linezolid. Alternatively, the intermediate 3-fluoro-4-morpholinoaniline was converted to the benzylcarbamate with benzyl chloroformate in aq. sodium bicarbonate, and subsequently treated with n-butyl lithium to form the anion and treated with (S)N-oxiranylmethyl)acetamide to provide linezolid.

Provenance & Evidence