N-(3-fluoro-4-hydroxyphenyl)acetamide

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

Procedure: A mixture of 2,4-dichloropyrimidine (Aldrich, 1.5 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (0.85 g, 5.0 mmol), K2CO3 (0.76 g, 5.5 mmol), and CH3CN (100 mL) was heated at reflux for 2 h. The mixture was concentrated and the residue partitioned between EtOAc and saturated NaHCO3 solution. The EtOAc phase was washed with sat NaHCO3 solution, brine, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography using a gradient form 30% EtOAc in hexanes to 100% EtOAc to give the title compound (1.1 g, 78%) as a white solid. 1H NMR (DMSO-d6) δ 10.22 (s, 1H), 8.63 (d, 1H, J=5.6 Hz), 7.74 (dd, 1H, J=12.6, 2.4 Hz), 7.34-7.26 (m, 3H), 2.01 (s, 3H). was heated at reflux for 2 h The mixture was concentrated the residue partitioned between EtOAc and saturated NaHCO3 solution The EtOAc phase was washed with sat NaHCO3 solution, brine dried (MgSO4) concentrated in vacuo The crude product was purified by flash chromatography

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4,6-dichloropyrimidine (1.50 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (1.70 g, 10.0 mmol), K2CO3 (1.8 g, 13.0 mmol), and DMF (15 mL) was heated at 70° C. for 1.5 h. The mixture was concentrated to half its original volume and cooled in an ice bath. The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration. The product was washed with H2O and vacuum dried on the funnel overnight to give the title compound (2.0 g, 71%) as a gray solid. 1H NMR (DMSO-d6) δ 10.26 (s, 1H), 8.67 (s, 1H), 7.78 (dd, 1H, J=12.6, 2.0 Hz), 7.56 (s, 1H), 7.37-7.30 (m, 2H), 2.08 (s, 3H); MS(ESI+) m/z 282.10 (M+H)+. The mixture was concentrated to half its original volume cooled in an ice bath The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration The product was washed with H2O and vacuum dried on the funnel overnight

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4,6-dichloropyrimidine (1.50 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (1.70 g, 10.0 mmol), K2CO3 (1.8 g, 13.0 mmol), and DMF (15 mL) was heated at 70° C. for 1.5 h. The mixture was concentrated to half its original volume and cooled in an ice bath. The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration. The product was washed with H2O and vacuum dried on the funnel overnight to give the title compound (2.0 g, 71%) as a gray solid. 1H NMR (DMSO-d6) δ 10.26 (s, 1H), 8.67 (s, 1H), 7.78 (dd, 1H, J=12.6, 2.0 Hz), 7.56 (s, 1H), 7.37-7.30 (m, 2H), 2.08 (s, 3H); MS(ESI+) m/z 282.10 (M+H)+. The mixture was concentrated to half its original volume cooled in an ice bath The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration The product was washed with H2O and vacuum dried on the funnel overnight

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4,6-dichloropyrimidine (1.50 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (1.70 g, 10.0 mmol), K2CO3 (1.8 g, 13.0 mmol), and DMF (15 mL) was heated at 70° C. for 1.5 h. The mixture was concentrated to half its original volume and cooled in an ice bath. The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration. The product was washed with H2O and vacuum dried on the funnel overnight to give the title compound (2.0 g, 71%) as a gray solid. 1H NMR (DMSO-d6) δ 10.26 (s, 1H), 8.67 (s, 1H), 7.78 (dd, 1H, J=12.6, 2.0 Hz), 7.56 (s, 1H), 7.37-7.30 (m, 2H), 2.08 (s, 3H); MS(ESI+) m/z 282.10 (M+H)+. The mixture was concentrated to half its original volume cooled in an ice bath The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration The product was washed with H2O and vacuum dried on the funnel overnight

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

Procedure: The title compound was prepared from the commercially available 2-fluoro-4-nitrophenol according the procedure of Burckhalter, J. H. et al. (J. Am. Chem. Soc. 1948, 70, 1363). Nitrophenol (5.73 g, 36.5 mmol) and acetic anhydride (3.72 g, 36.5 mmol) were dissolved in acetic acid (20 mL) and PtO2 (150 mg) was then added. The reaction mixture was shaken under H2 atmosphere (50 psi) at RT for 24 h. The precipitate which formed was collected by vacuum filtration and the filter paper was washed with acetic acid (25 mL). The combined filtrate and washing was concentrated in vacuo to give the title compound (2.0 g). The solid that remained on the filter paper was treated with MeOH to dissolve the product and the Pt2O filtered off. The filtrate was concentrated in vacuo and the solid obtained was triturated with 1:1 EtOAc/hexanes (200 mL) to give a second crop of the title compound (1.8 g, 62% overall). 1H NMR (DMSO-d6) δ 9.83 (s, 1H), 9.51 (s, 1H), 7.50 (dd, 1H, J=13.6, 2.5 Hz), 7.03 (d, 1H, J=8.5 Hz), 6.84 (dd, 1H, J=9.3, 9.3 Hz), 1.98 (s, 3H); MS(ESI+) m/z 170.23 (M+H)+. The precipitate which formed was collected by vacuum filtration the filter paper was washed with acetic acid (25 mL) The combined filtrate and washing was concentrated in vacuo

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

Procedure: A mixture of 2,4-dichloropyrimidine (Aldrich, 1.5 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (0.85 g, 5.0 mmol), K2CO3 (0.76 g, 5.5 mmol), and CH3CN (100 mL) was heated at reflux for 2 h. The mixture was concentrated and the residue partitioned between EtOAc and saturated NaHCO3 solution. The EtOAc phase was washed with sat NaHCO3 solution, brine, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography using a gradient form 30% EtOAc in hexanes to 100% EtOAc to give the title compound (1.1 g, 78%) as a white solid. 1H NMR (DMSO-d6) δ 10.22 (s, 1H), 8.63 (d, 1H, J=5.6 Hz), 7.74 (dd, 1H, J=12.6, 2.4 Hz), 7.34-7.26 (m, 3H), 2.01 (s, 3H). was heated at reflux for 2 h The mixture was concentrated the residue partitioned between EtOAc and saturated NaHCO3 solution The EtOAc phase was washed with sat NaHCO3 solution, brine dried (MgSO4) concentrated in vacuo The crude product was purified by flash chromatography

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4,6-dichloropyrimidine (1.50 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (1.70 g, 10.0 mmol), K2CO3 (1.8 g, 13.0 mmol), and DMF (15 mL) was heated at 70° C. for 1.5 h. The mixture was concentrated to half its original volume and cooled in an ice bath. The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration. The product was washed with H2O and vacuum dried on the funnel overnight to give the title compound (2.0 g, 71%) as a gray solid. 1H NMR (DMSO-d6) δ 10.26 (s, 1H), 8.67 (s, 1H), 7.78 (dd, 1H, J=12.6, 2.0 Hz), 7.56 (s, 1H), 7.37-7.30 (m, 2H), 2.08 (s, 3H); MS(ESI+) m/z 282.10 (M+H)+. The mixture was concentrated to half its original volume cooled in an ice bath The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration The product was washed with H2O and vacuum dried on the funnel overnight

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

Procedure: The title compound was prepared from the commercially available 2-fluoro-4-nitrophenol according the procedure of Burckhalter, J. H. et al. (J. Am. Chem. Soc. 1948, 70, 1363). Nitrophenol (5.73 g, 36.5 mmol) and acetic anhydride (3.72 g, 36.5 mmol) were dissolved in acetic acid (20 mL) and PtO2 (150 mg) was then added. The reaction mixture was shaken under H2 atmosphere (50 psi) at RT for 24 h. The precipitate which formed was collected by vacuum filtration and the filter paper was washed with acetic acid (25 mL). The combined filtrate and washing was concentrated in vacuo to give the title compound (2.0 g). The solid that remained on the filter paper was treated with MeOH to dissolve the product and the Pt2O filtered off. The filtrate was concentrated in vacuo and the solid obtained was triturated with 1:1 EtOAc/hexanes (200 mL) to give a second crop of the title compound (1.8 g, 62% overall). 1H NMR (DMSO-d6) δ 9.83 (s, 1H), 9.51 (s, 1H), 7.50 (dd, 1H, J=13.6, 2.5 Hz), 7.03 (d, 1H, J=8.5 Hz), 6.84 (dd, 1H, J=9.3, 9.3 Hz), 1.98 (s, 3H); MS(ESI+) m/z 170.23 (M+H)+. The precipitate which formed was collected by vacuum filtration the filter paper was washed with acetic acid (25 mL) The combined filtrate and washing was concentrated in vacuo

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

Procedure: A mixture of 2,4-dichloropyrimidine (Aldrich, 1.5 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (0.85 g, 5.0 mmol), K2CO3 (0.76 g, 5.5 mmol), and CH3CN (100 mL) was heated at reflux for 2 h. The mixture was concentrated and the residue partitioned between EtOAc and saturated NaHCO3 solution. The EtOAc phase was washed with sat NaHCO3 solution, brine, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography using a gradient form 30% EtOAc in hexanes to 100% EtOAc to give the title compound (1.1 g, 78%) as a white solid. 1H NMR (DMSO-d6) δ 10.22 (s, 1H), 8.63 (d, 1H, J=5.6 Hz), 7.74 (dd, 1H, J=12.6, 2.4 Hz), 7.34-7.26 (m, 3H), 2.01 (s, 3H). was heated at reflux for 2 h The mixture was concentrated the residue partitioned between EtOAc and saturated NaHCO3 solution The EtOAc phase was washed with sat NaHCO3 solution, brine dried (MgSO4) concentrated in vacuo The crude product was purified by flash chromatography

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4,6-dichloropyrimidine (1.50 g, 10.0 mmol), N-(3-fluoro-4-hydroxyphenyl)acetamide (1.70 g, 10.0 mmol), K2CO3 (1.8 g, 13.0 mmol), and DMF (15 mL) was heated at 70° C. for 1.5 h. The mixture was concentrated to half its original volume and cooled in an ice bath. The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration. The product was washed with H2O and vacuum dried on the funnel overnight to give the title compound (2.0 g, 71%) as a gray solid. 1H NMR (DMSO-d6) δ 10.26 (s, 1H), 8.67 (s, 1H), 7.78 (dd, 1H, J=12.6, 2.0 Hz), 7.56 (s, 1H), 7.37-7.30 (m, 2H), 2.08 (s, 3H); MS (ESI+) m/z 282.10 (M+H)+. The mixture was concentrated to half its original volume cooled in an ice bath The mixture was treated with H2O (100 mL) to precipitate the product which was collected by vacuum filtration The product was washed with H2O and vacuum dried on the funnel overnight

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

Procedure: The title compound was prepared from the commercially available 2-fluoro-4-nitrophenol according the procedure of Burckhalter, J. H. et al. (J. Am. Chem. Soc. 1948, 70, 1363). Nitrophenol (5.73 g, 36.5 mmol) and acetic anhydride (3.72 g, 36.5 mmol) were dissolved in acetic acid (20 mL) and PtO2 (150 mg) was then added. The reaction mixture was shaken under H2 atmosphere (50 psi) at RT for 24 h. The precipitate which formed was collected by vacuum filtration and the filter paper was washed with acetic acid (25 mL). The combined filtrate and washing was concentrated in vacuo to give the title compound (2.0 g). The solid that remained on the filter paper was treated with MeOH to dissolve the product and the Pt2O filtered off. The filtrate was concentrated in vacuo and the solid obtained was triturated with 1:1 EtOAc/hexanes (200 mL) to give a second crop of the title compound (1.8 g, 62% overall). 1H NMR (DMSO-d6) δ 9.83 (s, 1H), 9.51 (s, 1H), 7.50 (dd, 1H, J=13.6, 2.5 Hz), 7.03 (d, 1H, J=8.5 Hz), 6.84 (dd, 1H, J=9.3, 9.3 Hz), 1.98 (s, 3H); MS (ESI+) m/z 170.23 (M+H)+. The precipitate which formed was collected by vacuum filtration the filter paper was washed with acetic acid (25 mL) The combined filtrate and washing was concentrated in vacuo