4-bromo-2-chloro-1-methylsulfonylbenzene

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-chloro-1-methanesulfonyl-benzene (1.5 g, 5.6 mmol), 1-cyclopentyl-2-propen-1-ol (0.88 g, 6.96 mmol) and sodium acetate (0.57 g, 6.9 mmol) in DMAC (20 mL) was purged with N2 for 30 mins. Palladium (II) acetate (25 mg, 0.11 mmol) was added and the mixture was heated to 90° C. under N2 for 16 hours. The reaction mixture was partitioned between 1 N HCl and EtOAc. The organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to a brown oil. Purification by flash column chromatography (0% to 20% EtOAc in hexanes) gave the desired product (1.2 g, 69%). 1H NMR (300 MHz, CDCl3): δ 1.56–1.85 (br m, 8 H), 2.83 (m, 3 H), 2.96 (t, J=7.5 Hz, 2 H), 3.25 (s, 3 H), 7.29 (dd, J=8.1, 1.5 Hz, 1 H), 7.39 (d, J=1.5 Hz, 1 H), 8.04 (d, J=8.1 Hz, 1 H). was purged with N2 for 30 mins The reaction mixture was partitioned between 1 N HCl and EtOAc The organic layers were washed with saturated NaHCO3, brine dried over Na2SO4 concentrated to a brown oil Purification by flash column chromatography (0% to 20% EtOAc in hexanes)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-chloro-1-methanesulfonyl-benzene (1.5 g, 5.6 mmol), 1-cyclopentyl-2-propen-1-ol (0.88 g, 6.96 mmol) and sodium acetate (0.57 g, 6.9 mmol) in DMAC (20 mL) was purged with N2 for 30 mins. Palladium (II) acetate (25 mg, 0.11 mmol) was added and the mixture was heated to 90° C. under N2 for 16 hours. The reaction mixture was partitioned between 1 N HCl and EtOAc. The organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to a brown oil. Purification by flash column chromatography (0% to 20% EtOAc in hexanes) gave the desired product (1.2 g, 69%). 1H NMR (300 MHz, CDCl3): δ 1.56–1.85 (br m, 8 H), 2.83 (m, 3 H), 2.96 (t, J=7.5 Hz, 2 H), 3.25 (s, 3 H), 7.29 (dd, J=8.1, 1.5 Hz, 1 H), 7.39 (d, J=1.5 Hz, 1 H), 8.04 (d, J=8.1 Hz, 1 H). was purged with N2 for 30 mins The reaction mixture was partitioned between 1 N HCl and EtOAc The organic layers were washed with saturated NaHCO3, brine dried over Na2SO4 concentrated to a brown oil Purification by flash column chromatography (0% to 20% EtOAc in hexanes)

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

Procedure: Hydrazine monohydrate (1.51 mL, 48 mmol) was added to a cooled 0° C. solution of 4-bromo-2-chlorobenzenesulfonyl chloride (5 g, 17.2 mmol) dissolved in THF (50 mL). The reaction was stirred at room temperature for 2 hours and then the solvent was removed in vacuo to give a white solid. The solid was dissolved in EtOH (100 mL) and treated with sodium acetate (6.56 g, 80 mmol) followed by methyl iodide (4.9 mL, 79 mmol). The reaction mixture was refluxed for 18 hours. The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc. The organic layer was dried over MgSO4 and concentrated. The crude mixture was purified by flash column chromatography to give the product (1.5 g, 32%). 1H NMR (300 MHz, CDCl3): δ 3.26 (s, 3 H), 7.63 (dd, J=8.5, 1.9 Hz, 2 H), 7.74 (d, J=1.9 Hz, 1 H), 8.02 (d, J=8.5 Hz, 1 H). the solvent was removed in vacuo to give a white solid The reaction mixture was refluxed for 18 hours The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc The organic layer was dried over MgSO4 concentrated The crude mixture was purified by flash column chromatography

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

Procedure: Dissolve 4-bromo-2-chloro-1-methylsulfanyl-benzene (4.8 g, 20 mmol) and mCPBA (20 g, 80 mmol) in dichloromethane (100 mL). Stir for 2 hours. Dilute with dichloromethane (300 mL) and water (100 mL). Separate the organic layer and wash with aqueous saturated NaHCO3 (2×100 mL) and brine (100 mL). Dry with MgSO4, filter and concentrate in vacuo. Wash the solid with ether (2×14011) and dichloromethane (10 mL) to give 1.7 g of the title compound (31%). Separate the organic layer wash with aqueous saturated NaHCO3 (2×100 mL) and brine (100 mL) Dry with MgSO4 filter concentrate in vacuo Wash the solid with ether (2×14011) and dichloromethane (10 mL)

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

Procedure: Dissolve 4-bromo-2-chloro-1-methylsulfanyl-benzene (4.8 g, 20 mmol) and mCPBA (20 g, 80 mmol) in dichloromethane (100 mL). Stir for 2 hours. Dilute with dichloromethane (300 mL) and water (100 mL). Separate the organic layer and wash with aqueous saturated NaHCO3 (2×100 mL) and brine (100 mL). Dry with MgSO4, filter and concentrate in vacuo. Wash the solid with ether (2×14011) and dichloromethane (10 mL) to give 1.7 g of the title compound (31%). Separate the organic layer wash with aqueous saturated NaHCO3 (2×100 mL) and brine (100 mL) Dry with MgSO4 filter concentrate in vacuo Wash the solid with ether (2×14011) and dichloromethane (10 mL)

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

Procedure: Dissolve 4-bromo-2-chloro-1-methylsulfanyl-benzene (4.8 g, 20 mmol) and mCPBA (20 g, 80 mmol) in dichloromethane (100 mL). Stir for 2 hours. Dilute with dichloromethane (300 mL) and water (100 mL). Separate the organic layer and wash with aqueous saturated NaHCO3 (2×100 mL) and brine (100 mL). Dry with MgSO4, filter and concentrate in vacuo. Wash the solid with ether (2×10 mL) and dichloromethane (10 mL) to give 1.7 g of the title compound (31%). Separate the organic layer wash with aqueous saturated NaHCO3 (2×100 mL) and brine (100 mL) Dry with MgSO4 filter concentrate in vacuo Wash the solid with ether (2×10 mL) and dichloromethane (10 mL)

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

Procedure: Hydrazine monohydrate (1.51 mL, 48 mmol) was added to a cooled 0° C. solution of 4-bromo-2-chlorobenzenesulfonyl chloride (5 g, 17.2 mmol) dissolved in THF (50 mL). The reaction was stirred at room temperature for 2 hours and then the solvent was removed in vacuo to give a white solid. The solid was dissolved in EtOH (100 mL) and treated with sodium acetate (6.56 g, 80 mmol) followed by methyl iodide (4.9 mL, 79 mmol). The reaction mixture was refluxed for 18 hours. The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc. The organic layer was dried over MgSO4 and concentrated. The crude mixture was purified by flash column chromatography to give the product (1.5 g, 32%). 1H NMR (300 MHz, CDCl3): δ 3.26 (s, 3H), 7.63 (dd, J=8.5, 1.9 Hz, 2 H), 7.74 (d, J=1.9 Hz, 1 H), 8.02 (d, J=8.5 Hz, 1 H). the solvent was removed in vacuo to give a white solid The reaction mixture was refluxed for 18 hours The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc The organic layer was dried over MgSO4 concentrated The crude mixture was purified by flash column chromatography

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

Procedure: Hydrazine monohydrate (1.51 mL, 48 mmol) was added to a cooled 0° C. solution of 4-bromo-2-chlorobenzenesulfonyl chloride (5 g, 17.2 mmol) dissolved in THF (50 mL). The reaction was stirred at room temperature for 2 hours and then the solvent was removed in vacuo to give a white solid. The solid was dissolved in EtOH (100 mL) and treated with sodium acetate (6.56 g, 80 mmol) followed by methyl iodide (4.9 mL, 79 mmol). The reaction mixture was refluxed for 18 hours. The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc. The organic layer was dried over MgSO4 and concentrated. The crude mixture was purified by flash column chromatography to give the product (1.5 g, 32%). 1H NMR (300 MHz, CDCl3): δ 3.26 (s, 3H), 7.63 (dd, J=8.5, 1.9 Hz, 2 H), 7.74 (d, J=1.9 Hz, 1 H), 8.02 (d, J=8.5 Hz, 1 H). the solvent was removed in vacuo to give a white solid The reaction mixture was refluxed for 18 hours The solvent was removed in vacuo to give a residue that was partitioned between 1 N HCl and EtOAc The organic layer was dried over MgSO4 concentrated The crude mixture was purified by flash column chromatography

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

Procedure: The compound of Production Example 160 was obtained as a white amorphous substance using 5-hydroxy-3-methoxymethoxybenzoic acid methyl ester, 4-bromo-2-chloro-methanesulfonylbenzene, (2R)-1-(t-butyldimethylsiloxy)-2-hydroxypropane and 3-amino-1-methyl-1H-pyrazole, by the same method as in Production Example 42, a corresponding method, or a combination thereof with an ordinary method. The compound of Production Example 160 was obtained as a white amorphous substance

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

Procedure: The compound of Production Example 160 was obtained as a white amorphous substance using 5-hydroxy-3-methoxymethoxybenzoic acid methyl ester, 4-bromo-2-chloro-methanesulfonylbenzene, (2R)-1-(t-butyldimethylsiloxy)-2-hydroxypropane and 3-amino-1-methyl-1H-pyrazole, by the same method as in Production Example 42, a corresponding method, or a combination thereof with an ordinary method. The compound of Production Example 160 was obtained as a white amorphous substance

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

Procedure: The compound of Production Example 160 was obtained as a white amorphous substance using 5-hydroxy-3-methoxymethoxybenzoic acid methyl ester, 4-bromo-2-chloro-methanesulfonylbenzene, (2R)-1-(t-butyldimethylsiloxy)-2-hydroxypropane and 3-amino-1-methyl-1H-pyrazole, by the same method as in Production Example 42, a corresponding method, or a combination thereof with an ordinary method. The compound of Production Example 160 was obtained as a white amorphous substance

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-chloro-1-methanesulfonyl-benzene (1.5 g, 5.6 mmol), 1-cyclopentyl-2-propen-1-ol (0.88 g, 6.96 mmol) and sodium acetate (0.57 g, 6.9 mmol) in DMAC (20 mL) was purged with N2 for 30 mins. Palladium (II) acetate (25 mg, 0.11 mmol) was added and the mixture was heated to 90° C. under N2 for 16 hours. The reaction mixture was partitioned between 1 N HCl and EtOAc. The organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to a brown oil. Purification by flash column chromatography (0% to 20% EtOAc in hexanes) gave the desired product (1.2 g, 69%). 1H NMR (300 MHz, CDCl3): δ 1.56-1.85 (br m, 8H), 2.83 (m, 3H), 2.96 (t, J=7.5 Hz, 2H), 3.25 (s, 3H), 7.29 (dd, J=8.1, 1.5 Hz, 1H), 7.39 (d, J=1.5 Hz, 1H), 8.04 (d, J=8.1 Hz, 1H). was purged with N2 for 30 mins The reaction mixture was partitioned between 1 N HCl and EtOAc The organic layers were washed with saturated NaHCO3, brine dried over Na2SO4 concentrated to a brown oil Purification by flash column chromatography (0% to 20% EtOAc in hexanes)