2-iodophenol

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

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

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

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

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

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

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

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

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

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-iodophenol (8.0 g, 36.4 mmol), milled potassium carbonate (5.5 g, 39.9 mmol, 1.1 eq) and 1-bromocyclopentane bromide (3.9 ml, 36.4 mmol) in 25 ml of N,N-dimethylformamide was heated at 120° C. for 1.1 hrs and cooled. The mixture was poured into water and extracted twice with ether. The ether layer was dried over magnesium sulfate, filtered, and concentrated to give an oil. The crude product was dissolved in ethyl acetate and filtered through a short pad of silica gel. The filtrate was redried over magnesium sulfate, filtered and concentrated under vacuum to give 10 g (95%) of product as an oil. cooled extracted twice with ether The ether layer was dried over magnesium sulfate filtered concentrated to give an oil filtered through a short pad of silica gel The filtrate was redried over magnesium sulfate filtered concentrated under vacuum

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

Procedure: 4-Picolyl chloride hydrochloride (4.00 g, 24.4 mmol) was dissolved in acetone (55 mL), potassium carbonate (10.1 g, 73.2 mmol) and o-iodophenol (6.97 g, 31.7 mmol) were added, and the mixture was heated under reflux for 24 hr. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added to the obtained crystals, and the mixture was suction-filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2) to give the title compound (4.02 g, 53%). the mixture was heated under reflux for 24 hr The reaction mixture was concentrated under reduced pressure, ethyl acetate was added to the obtained crystals the mixture was suction-filtered The filtrate was concentrated under reduced pressure the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2)

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

Procedure: To a stirred solution of the 2-iodophenol (220.0 mg, 1.0 mmol), the 2-(2-(trifluoromethyl)phenyl)ethanol (228.0 mg, 1.2 mmol), and triphenyl phosphine (314.0 mg, 1.2 mmol) in anhydrous THF (5 mL) at 0° C. was added DEAD (40% in toluene, 1.20 mmol, 0.35 mL) dropwise. The yellow solution was allowed to warm to room temperature and stirring was continued overnite. After evaporating the solvent under reduced pressure the crude residue was dissolved in DCM (15 mL). The organic layer was washed with 10% NaOH (2×10 mL), water and brine. The organic phase was dried (Na2SO4), filtered and evaporated under reduced pressure. The crude residue was purified by column chromatography on silica gel using hexanes/EtOAc as the eluent. The compound was isolated in 56% yield as a white solid. 1H NMR: 3.17 (t, 2H, J=6.8 Hz), 4.22 (t, 2H, J=6.8 Hz), 6.90-7.10 (m, 4H), 7.15-7.23 (m 1H), 7.30-7.45 (m, 2H), 7.74 (dd, 1H, J=7.6, 1.6 Hz). After evaporating the solvent under reduced pressure the crude residue was dissolved in DCM (15 mL) The organic layer was washed with 10% NaOH (2×10 mL), water and brine The organic phase was dried (Na2SO4) filtered evaporated under reduced pressure The crude residue was purified by column chromatography on silica gel The compound was isolated in 56% yield as a white solid