1-(3-fluoro-4-hydroxyphenyl)propan-1-one

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-fluorophenol (1.0 g, 5.24 mmol) in tetrahydrofuran (15 mL) was chilled to -78° C. and butyllithium (4.6 mL, 11.5 mmol, 2.5 M solution) was added rapidly, dropwise. The reaction was stirred 12 min and N-methyl-N-methoxypropionamide (the compound of Preparation 9 , 0.735 g, 6.28 mmol in 1 mL of tetrahydrofuran with a 1 mL rinse) was added. The reaction was allowed to stir 5 min at -78° C. and then it was warmed to ambient temperature. A few drops of water were added; then the solvent was removed at reduced pressure. The residue was taken up in methylene chloride and washed with aqueous ammonium chloride and brine. The organic layer was dried and concentrated. The residue was flash chromatographed on silica gel (1×2.5 inches packed in hexane) with elution proceeding as follows: 10% ethyl acetate/hexane (250 mL), discarded forerun; 20% ethyl acetate/hexane (250 mL), 0.186 g of a yellow crystalline solid which had NMR identical to that of preparation 7. rinse) was added to stir 5 min at -78° C. it was warmed to ambient temperature A few drops of water were added then the solvent was removed at reduced pressure washed with aqueous ammonium chloride and brine The organic layer was dried concentrated chromatographed on silica gel (1×2.5 inches packed in hexane) with elution proceeding of preparation 7

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

Procedure: Following general procedure of McMurry reaction as described in example 1, step B, 1-(3-fluoro-4-hydroxyphenyl)propan-1-one (255 mg, 1.52 mmol) was reacted with (4-(2-chloroethoxy)phenyl)(4-hydroxyphenyl)methanone (629 mg, 2.27 mmol) to give 549 mg desired product (88% yield). general procedure of McMurry reaction

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

Procedure: 1-(3-Fluoro-4-methoxyphenyl)propan-1-one (421 mg, 2.31 mmol) in 20 mL 40% HBr was refluxed for 1 h., neutralized with solid Na2CO3 at 0° C., and extracted with EtOAc. The extract was washed with brine, dried, concentrated, and purified by column chromatography (eluent: petroleum ether/EtOAc=5/1) over silica gel to give the product (257 mg, 66% yield) as a yellow solid. extracted with EtOAc The extract was washed with brine dried concentrated purified by column chromatography (eluent: petroleum ether/EtOAc=5/1) over silica gel

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

Procedure: 1-(3-Fluoro-4-methoxyphenyl)propan-1-one (421 mg, 2.31 mmol) in 20 mL 40% HBr was refluxed for 1 h., neutralized with solid Na2CO3 at 0° C., and extracted with EtOAc. The extract was washed with brine, dried, concentrated, and purified by column chromatography (eluent: petroleum ether/EtOAc=5/1) over silica gel to give the product (257 mg, 66% yield) as a yellow solid. extracted with EtOAc The extract was washed with brine dried concentrated purified by column chromatography (eluent: petroleum ether/EtOAc=5/1) over silica gel

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-fluorophenol (1.0 g, 5.24 mmol) in tetrahydrofuran (15 mL) was chilled to −78° C. and butyllithium (4.6 mL, 11.5 mmol, 2.5 M solution) was added rapidly, dropwise. The reaction was stirred 12 min and N-methyl-N-methoxypropionamide (the compound of Preparation 9, 0.735 g, 6.28 mmol in 1 mL of tetrahydrofuran with a 1 mL rinse) was added. The reaction was allowed to stir 5 min at −78° C. and then it was warmed to ambient temperature. A few drops of water were added; then the solvent was removed at reduced pressure. The residue was taken up in methylene chloride and washed with aqueous ammonium chloride and brine. The organic layer was dried and concentrated. The residue was flash chromatographed on silica gel (1×2.5 inches packed in hexane) with elution proceeding as follows: 10% ethyl acetate/hexane (250 mL), discarded forerun; 20% ethyl acetate/hexane (250 mL), 0.186 g of a yellow crystalline solid which had NMR identical to that of preparation 7. rinse) was added to stir 5 min at −78° C. it was warmed to ambient temperature A few drops of water were added then the solvent was removed at reduced pressure washed with aqueous ammonium chloride and brine The organic layer was dried concentrated chromatographed on silica gel (1×2.5 inches packed in hexane) with elution proceeding of preparation 7

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-fluorophenol (1.0 g, 5.24 mmol) in tetrahydrofuran (15 mL) was chilled to -78° C. and butyllithium (4.6 mL, 11.5 mmol, 2.5 M solution) was added rapidly, dropwise. The reaction was stirred 12 min and N-methyl-N-methoxypropionamide (the compound of Preparation 9 , 0.735 g, 6.28 mmol in 1 mL of tetrahydrofuran with a 1 mL rinse) was added. The reaction was allowed to stir 5 min at -78° C. and then it was warmed to ambient temperature. A few drops of water were added; then the solvent was removed at reduced pressure. The residue was taken up in methylene chloride and washed with aqueous ammonium chloride and brine. The organic layer was dried and concentrated. The residue was flash chromatographed on silica gel (1×2.5 inches packed in hexane) with elution proceeding as follows: 10% ethyl acetate/hexane (250 mL), discarded forerun; 20% ethyl acetate/hexane (250 mL), 0.186 g of a yellow crystalline solid which had NMR identical to that of preparation 7. rinse) was added to stir 5 min at -78° C. it was warmed to ambient temperature A few drops of water were added then the solvent was removed at reduced pressure washed with aqueous ammonium chloride and brine The organic layer was dried concentrated chromatographed on silica gel (1×2.5 inches packed in hexane) with elution proceeding of preparation 7

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

Procedure: Following general procedure of McMurry reaction as described in example 1, step B, 1-(3-fluoro-4-hydroxyphenyl)propan-1-one (255 mg, 1.52 mmol) was reacted with (4-(2-chloroethoxy)phenyl)(4-hydroxyphenyl)methanone (629 mg, 2.27 mmol) to give 549 mg desired product (88% yield). general procedure of McMurry reaction

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

Procedure: 1-(3-Fluoro-4-methoxyphenyl)propan-1-one (421 mg, 2.31 mmol) in 20 mL 40% HBr was refluxed for 1 h., neutralized with solid Na2CO3 at 0° C., and extracted with EtOAc. The extract was washed with brine, dried, concentrated, and purified by column chromatography (eluent: petroleum ether/EtOAc=5/1) over silica gel to give the product (257 mg, 66% yield) as a yellow solid. extracted with EtOAc The extract was washed with brine dried concentrated purified by column chromatography (eluent: petroleum ether/EtOAc=5/1) over silica gel