1-bromo-2-cyclohexyloxybenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: NaH (8.4 g, 210 mmol, 60% in mineral oil) was slurred in DMF (40 mL) and heated to about 65° C. To the slurry was added cyclohexanol (7 g, 69.9 mmol) dissolved in DMF (50 mL). The mixture was stirred at 65° C. for about 1 hour. Ortho-fluoro bromobenzene (9.2 mL, 83.9 mmol) was added dropwise in DMF (10 mL) and the mixture was stirred at 65° C. for about 16 hours, and quenched with water and diluted with DCM. The mixture was concentrated to an oily solid and extracted between water and 1/1 EtOAc/hex. The organic layer was dried, filtered and concentrated. Chromatography on silica gel (EtOAc/hexanes) gave 1-bromo-2-cyclohydroxy-benzene (6.13 g, 34%) as a yellow oil. 1-Bromo-2-cyclohexyloxy-benzene was coupled to piperazine using the Buchwald chemistry described in preparation 1A. LRMS (ESI+): 261.1 (M+1)