tert-butyl N-(3-fluoro-4-hydroxyphenyl)carbamate

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: The entitled compound was obtained in the same method as in Example 221 (step 1) or in accordance with the method or by combining it with an ordinary method but using tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate obtained in Example 196 (step 1) and 1,2-difluoro-3-cyano-benzene. The entitled compound was obtained in the same method as in Example 221 (step 1) or in accordance with the method

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10.9 g of 5-chloro-2-ethanesulfonyl-pyridine and 1.6 g of cesium carbonate were added to a dimethylformamide (150 ml) solution of 10.0 g of tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate obtained in Example 196 (step 1), and the reaction liquid was stirred at 100° C. for 3 hours. The solvent was evaporated away under reduced pressure, diluted with chloroform, washed with aqueous saturated sodium bicarbonate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/9) to obtain a crude product. The resulting crude product was dissolved in 4 N hydrochloric acid/dioxane, and stirred at room temperature for 1 hour. The solvent was evaporated away under reduced pressure, diluted with chloroform, washed with water, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/9) to obtain the entitled compound. the reaction liquid The solvent was evaporated away under reduced pressure diluted with chloroform washed with aqueous saturated sodium bicarbonate dried with anhydrous sodium sulfate The solvent was evaporated away under reduced pressure the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/9)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4.00 g of 5-chloro-2-methanesulfonyl-pyridine and 8.80 g of cesium carbonate were added to an N-methylpyrrolidinone (50 ml) solution of 4.74 g of tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate obtained in (step 1), and the reaction liquid was stirred at 100° C. for 2 hours. The reaction liquid was diluted with ethyl acetate, washed with water and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the entitled compound. obtained in (step 1) the reaction liquid The reaction liquid washed with water and saturated saline in order dried with anhydrous sodium sulfate The solvent was evaporated away under reduced pressure the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the entitled compound

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

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

Procedure: The entitled compound was obtained in the same method as in Example 221 (step 1) or in accordance with the method or by combining it with an ordinary method but using tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate obtained in Example 196 (step 1) and 1,2-difluoro-3-cyano-benzene. The entitled compound was obtained in the same method as in Example 221 (step 1) or in accordance with the method

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10.9 g of 5-chloro-2-ethanesulfonyl-pyridine and 1.6 g of cesium carbonate were added to a dimethylformamide (150 ml) solution of 10.0 g of tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate obtained in Example 196 (step 1), and the reaction liquid was stirred at 100° C. for 3 hours. The solvent was evaporated away under reduced pressure, diluted with chloroform, washed with aqueous saturated sodium bicarbonate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/9) to obtain a crude product. The resulting crude product was dissolved in 4 N hydrochloric acid/dioxane, and stirred at room temperature for 1 hour. The solvent was evaporated away under reduced pressure, diluted with chloroform, washed with water, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/9) to obtain the entitled compound. the reaction liquid The solvent was evaporated away under reduced pressure diluted with chloroform washed with aqueous saturated sodium bicarbonate dried with anhydrous sodium sulfate The solvent was evaporated away under reduced pressure the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/9)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4.00 g of 5-chloro-2-methanesulfonyl-pyridine and 8.80 g of cesium carbonate were added to an N-methylpyrrolidinone (50 ml) solution of 4.74 g of tert-butyl (3-fluoro-4-hydroxy-phenyl)-carbamate obtained in (step 1), and the reaction liquid was stirred at 100° C. for 2 hours. The reaction liquid was diluted with ethyl acetate, washed with water and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the entitled compound. obtained in (step 1) the reaction liquid The reaction liquid washed with water and saturated saline in order dried with anhydrous sodium sulfate The solvent was evaporated away under reduced pressure the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1) to obtain the entitled compound

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

Procedure: A solution of N-Boc-4-amino-2-fluorophenol (228 mg, 1.0 mmol) in DMF (2 mL) was treated with t-BuOK (124 mg, 1.1 mmol) and the mixture stirred at room temperature for 2 h. The mixture was treated with 4-chloropyridine-2,6-dicarboxamide (200 mg, 1.0 mmol) and K2CO3 (35 mg, 0.5 mmol) and heated at 80° C. for 1.5 h. The mixture was concentrated in vacuo, treated with EtOAc (10 mL) and H2O (10 mL) and filtered to remove the insoluble material. The EtOAc phase was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the residue by flash column chromatography on SiO2 eluting with 30-100% EtOAc/hexanes gave the title compound (170 mg, 44%) as a white solid containing 10% of the starting chloropyridine. 1H NMR (DMSO-d6) δ 9.77 (s, 1H), 8.86 (s, 2H), 7.87 (s, 1H), 7.63 (d, 1H, J=12.1 Hz), 7.55 (s, 2H), 7.38-7.31 (m, 2H), 1.48 (s, 9H). heated at 80° C. for 1.5 h The mixture was concentrated in vacuo treated with EtOAc (10 mL) and H2O (10 mL) filtered to remove the insoluble material The EtOAc phase was washed with brine dried (MgSO4) concentrated in vacuo Purification of the residue by flash column chromatography on SiO2 eluting with 30-100% EtOAc/hexanes