2-(3-fluoro-4-methoxyphenyl)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: A mixture of resin bound triphenyl phosphine (polystyrene 2% cross linking, loading=3 mmol/g, 3 g, 9 mmol) and imidazole (0.48 g, 7.1 mmol) in DCM (30 mL) cooled on an ice bath was drop wise added Br2 (1.13 g, 7.1 mmol), whereupon a solution of 4-(2-hydroxy-ethyl)-2-fluoro-1-methoxy-benzene (1.0 g, 5.88 mmol) in DCM (5 mL) was added. The cooling bath was removed and the reaction mixture was stirred for 16 hs before the resin was filtered off. The resin was washed with DCM and the filtrate was concentrated in vacuo. The residue was purified using column chromatography (SiO2, heptane-EtAOc 95:5) to give 0.82 g of 4-(2-bromo-ethyl)-2-fluoro-1-methoxy-benzene A mixture of resin cooled on an ice bath The cooling bath was removed was filtered off The resin was washed with DCM the filtrate was concentrated in vacuo The residue was purified

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

Procedure: A mixture of resin bound triphenyl phosphine (polystyrene 2% cross linking, loading =3 mmol/g, 3 g, 9 mmol) and imidazole (0.48 g, 7.1 mmol) in DCM (30 mL) cooled on an ice bath was drop wise added Br2 (1.13 g, 7.1 mmol), whereupon a solution of 4-(2-hydroxy-ethyl) -2-fluoro-1-methoxy-benzene (1.0 g, 5.88 mmol) in DCM (5 mL) was added. The cooling bath was removed and the reaction mixture was stirred for 16 hs before the resin was filtered off. The resin was washed with DCM and the filtrate was concentrated in vacuo. The residue was purified using column chromatography (SiO2, heptane-EtAOc 95:5) to give 0.82 g of 4-(2-bromo-ethyl)-2-fluoro-1-methoxy-benzene A mixture of resin cooled on an ice bath The cooling bath was removed was filtered off The resin was washed with DCM the filtrate was concentrated in vacuo The residue was purified

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

Procedure: To a solution of 4-[2-(4-hydroxymethyl-2-methyl-4,5-dihydro-oxazol-4-yl)-ethyl]-phenol (300 mg, 1.27 mmol) in dry THF (6 ml) is added under inert atmosphere polystyrene supported triphenylphosphine (loading 3 mmol·g−1, 1.27 g, 3.81 mmol, 3 eq.), 2-(3-fluoro-4-methoxyphenyl)-ethanol (647.7 mg, 3.81 mmol, 3 eq.) and DBAD (877.3 mg, 3.81 mmol, 3 eq.). The reaction mixture was stirred under inert atmosphere at room temperature overnight. Polystyrene supported triphenylphosphine was then filtered through frit and washed with ethyl acetate and methanol. The reaction mixture was then concentrated to dryness following by addition of 4M HCl in dioxane (3 ml), the reaction was stirred at room temperature for 3 hours. The reaction mixture was quenched by addition of saturated solution of NaHCO3 (10 ml) and ethyl acetate (40 ml). The organic layer is separated and the aqueous phase is extracted with ethyl acetate (3×40 ml). The combined organic extracts are washed with brine, dried over MgSO4, and evaporated to dryness. Purification using Flashmaster (chexane/ethyl acetate (1/9), ethyl acetate and ethyl acetate/methanol (98/2)) affords [4-(2-{4-[2-(3-fluoro-4-methoxy-phenyl)-ethoxy]-phenyl}ethyl)-2-methyl-4,5-dihydro-oxazol-4-yl]-methanol as colorless oil. MS (ESI+): 364.2 (MH+) was then filtered through frit washed with ethyl acetate and methanol The reaction mixture was then concentrated to dryness following by addition of 4M HCl in dioxane (3 ml) the reaction was stirred at room temperature for 3 hours The reaction mixture was quenched by addition of saturated solution of NaHCO3 (10 ml) and ethyl acetate (40 ml) The organic layer is separated the aqueous phase is extracted with ethyl acetate (3×40 ml) The combined organic extracts are washed with brine dried over MgSO4 evaporated to dryness Purification

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