1-(4-chloro-3-fluorophenyl)ethanol

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: To a solution of the above alcohol (1 eq) in CH2Cl2 (0.3M) at rt was added Dess-Martin periodinane (1.5 eq). The reaction mixture was stirred for 45 minutes at rt and H2O (10 eq) was added. The mixture was stirred for 30 minutes and filtered through silica gel pad eluted with 30% EtOAc/hexane and concentrated. The residue was purified by flash chromatography on silica gel eluted with 20% EtOAc/hexane to give the title compound. The mixture was stirred for 30 minutes filtered through silica gel pad eluted with 30% EtOAc/hexane concentrated The residue was purified by flash chromatography on silica gel eluted with 20% EtOAc/hexane

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-3-fluorobenzaldehyde (1 eq) in THF (0.3 M) at −78° C. was added 3M/Et2O MeMgBr (1.5 eq). The reaction mixture was stirred at −50° C. for 3 hrs, quenched with aqueous saturated NH4Cl and extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated to give 1-(4-chloro-3-fluorophenyl)ethanol, which was used as such for the next step. quenched with aqueous saturated NH4Cl extracted with EtOAc The combined organic layers were dried over Na2SO4 concentrated

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

Procedure: Methylmagnesium bromide (22.5 mL, 31.5 mmol; 1.4 M solution in toluene/tetrahydrofuran) was added dropwise to a solution of 4-chloro-3-fluorobenzaldehyde (5.0 g, 31.5 mmol) in 100 mL of dry tetrahydrofuran at −78° C. over 15 min. The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into saturated NH4Cl (100 mL). The aqueous layer was extracted with diethyl ether (3×150 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 1-(4-chloro-3-fluorophenyl)ethanol (5.50 g, 100%) as a yellow oil which was used in the next step without further purification, MS (ES) m/z 175 [M+H+]. The aqueous layer was extracted with diethyl ether (3×150 mL) The organic layer was dried over anhydrous sodium sulfate filtered concentrated in vacuo

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

Procedure: 4-Chloro-3-fluoro-benzaldehyde (5.14 g, 32.4 mmol) was dissolved in THF (100 mL) and place at −78° C. under nitrogen atmosphere. Methyl Lithium (1.6 M in diethyl ether, 22.3 mL) was added to the reaction during a period of 3 minutes maintianing the same temperature. After the addition, the reaction was stirred at room temperature for 1 h. Then, the reaction was poured over ice water and extracted with ethyl acetate and hydrochloric acid 1N. The organic layer was collected, dried with sodium sulfate, filtered and concentrated under vacuum to produce a crude, which it was chromatograph over silica gel using 50% hexane-ethyl Acetate as solvent to yield 5.1 g of 1-(4-chloro-3-fluoro-phenyl)-ethanol. 1H NMR (400 MHz, Cl3CD) δ 7.37 (t, J=8.14 Hz, 1H), 7.20 (dd, J=1.86, 10.00 Hz, 1H), 7.09 (dd, J=1.86, 8.14 Hz, 1H), 4.89 (m, 1H), 1.93 (br s, 1H), 1.49 (d, J=6.51, 3H). at −78° C. After the addition extracted with ethyl acetate and hydrochloric acid 1N The organic layer was collected dried with sodium sulfate filtered concentrated under vacuum to produce a crude, which it