ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate

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: A mixture of 1′-[4-(bromomethyl)benzyl]-2,3-dihydrospiro[indene-1,4′-piperidine] (0.35 g, 0.94 mmol), ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate (0.2 g, 0.94 mmol) and K2CO3 (0.32 g, 2.3 mmol) in DMF (15 mL) is stirred overnight at room temperature. The reaction mixture is diluted with cold water and extracted with DCM (3×50 mL). The combined organic layer is washed with brine solution, dried over Na2SO4, and concentrated under vacuum. The crude material is purified by silica gel chromatography (gradient DCM/MeOH 8/2) to give the title compound as an off-white solid (0.22 g, crude). ESI/MS 502 (M+H)+. extracted with DCM (3×50 mL) The combined organic layer is washed with brine solution dried over Na2SO4 concentrated under vacuum The crude material is purified by silica gel chromatography (gradient DCM/MeOH 8/2)

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 4-({[3′-(hydroxymethyl)-2,6-dimethylbiphenyl-4-yl]oxy}methyl)tetrahydro-2H-thiopyran-4-ol (0.90 g, 2.51 mmol), ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate (0.56 g, 2.64 mmol) and tributylphosphine (0.86 mL, 3.26 mmol) in tetrahydrofuran (20 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.85 g, 3.26 mmol) at room temperature with stirring, and the mixture was stirred for 10 hrs. The resulting precipitate was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1) to give the title compound (1.24 g, yield 89%) as a colorless oil. the mixture was stirred for 10 hrs The resulting precipitate was filtered off the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1)

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

Procedure: To a solution of 4-({[3′-(hydroxymethyl)-2,6-dimethylbiphenyl-4-yl]oxy}methyl)tetrahydro-2H-thiopyran-4-ol (0.90 g, 2.51 mmol), ethyl 3-(2-fluoro-4-hydroxyphenyl)propanoate (0.56 g, 2.64 mmol) and tributylphosphine (0.86 mL, 3.26 mmol) in tetrahydrofuran (20 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.85 g, 3.26 mmol) at room temperature with stirring, and the mixture was stirred for 10 hrs. The resulting precipitate was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1) to give the title compound (1.24 g, yield 89%) as a colorless oil. the mixture was stirred for 10 hrs The resulting precipitate was filtered off the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=2/1)

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

Procedure: To a solution of ethyl 3-(2-fluoro-4-methoxyphenyl)propanoate (57.4 g, 254 mmol) and aluminum chloride (101 g, 761 mmol) in dichloromethane (250 mL) was added dropwise 1-octanethiol (74.3 g, 508 mmol) and the mixture was stirred at room temperature for 2 hrs. The reaction mixture was poured into ice water and the mixture was stirred for 30 min. The organic layer was separated, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20% ethyl acetate/hexane) to give the title compound (44.6 g, yield 83%) as a colorless oil. the mixture was stirred for 30 min The organic layer was separated washed with saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (20% ethyl acetate/hexane)