(3,5-dichlorophenyl)methanol

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

Procedure: To a solution of 3.5 g of 3,5-dichlorobenzyl alcohol (Aldrich) in 75 mL of dichloromethane at 0° C. was added 1.8 mL of methane sulfonylchloride followed by 3.5 mL of triethylamine added dropwise. After 2 hours the solution was diluted to 150 mL with dichloromethane, washed with 3N HCl, saturated aqueous NaHCO3 dried with Na2SO4 and the solvents removed to yield the desired 3,5-dichlorobenzyl methanesulfonate as a yellow oil that was used without purification. added dropwise washed with 3N HCl, saturated aqueous NaHCO3 dried with Na2SO4 the solvents removed

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

Procedure: Using essentially the same coupling procedure as for Example 8-1, Step 1, but heating 2,4-difluorophenylboronic acid (456 mg, 2.89 mmol) and 3,5-dichloro-4-iodobenzyl alcohol (350 mg, 1.155 mmol) in a microwave at 115° C. for 120 minutes, afforded the title intermediate (242 mg) without formation of any appreciable 3,5-dichlorobenzyl alcohol.

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

Procedure: To a solution of 2,6-dichloro-4′-fluorobiphenyl-4-carboxylic acid (350 mg, 1.155 mmol) in THF (5 mL) was added 2M borane-methyl sulfide complex in THF (0.35 mL, 0.70 mmol) at room temperature. After 20 hours, the reaction was quenched with 2M HCl and water and was extracted twice with ethyl acetate. The organic layers were washed with brine containing some aqueous sodium bicarbonate, dried over sodium sulfate, combined and concentrated. The residue was purified on silica gel (COMBI FLASH 12 gm column, 100% DCM, then a gradient of 2-10% ethyl acetate/DCM) to give a single main band by TLC (65 mg) containing a 1:1 mixture of title intermediate and 3,5-dichlorobenzyl alcohol from the Step 1 bi-product impurity. The mixture was used directly in Step 3. the reaction was quenched with 2M HCl and water was extracted twice with ethyl acetate The organic layers were washed with brine containing some aqueous sodium bicarbonate dried over sodium sulfate concentrated The residue was purified on silica gel (COMBI FLASH 12 gm column, 100% DCM a gradient of 2-10% ethyl acetate/DCM) to give a single main band by TLC (65 mg) containing