4-butan-2-ylphenol

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

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

Procedure: 4-sec-Butyl-phenol (3.0 g) is dissolved in chloroform and thereto is added bromine (1.02 ml) and the mixture is stirred at room temperature for 30 minutes. Thereto are added a saturated aqueous sodium thiosulfate solution, a saturated aqueous sodium bicarbonate solution and ethyl acetate, and the mixture is separated. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give 2-bromo-4-sec-butyl-phenol (4.57 g). NMR (CDCl3): 0.81 (3H, t), 1.19 (3H, d), 1.56 (2H, m), 2.51 (1H, m), 5.33 (1H, s), 6.93 (1H, d), 7.02 (1H, d), 7.26 (1H, s). a saturated aqueous sodium bicarbonate solution and ethyl acetate, and the mixture is separated The organic layer is washed with a saturated brine dried over magnesium sulfate concentrated under reduced pressure

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

Procedure: 4-sec-Butyl-phenol (3.0 g) is dissolved in chloroform and thereto is added bromine (1.02 ml) and the mixture is stirred at room temperature for 30 minutes. Thereto are added a saturated aqueous sodium thiosulfate solution, a saturated aqueous sodium bicarbonate solution and ethyl acetate, and the mixture is separated. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give 2-bromo-4-sec-butyl-phenol (4.57 g). NMR (CDCl3): 0.81 (3H, t), 1.19 (3H, d), 1.56 (2H, m), 2.51 (1H, m), 5.33 (1H, s), 6.93 (1H, d), 7.02 (1H, d), 7.26 (1H, s). a saturated aqueous sodium bicarbonate solution and ethyl acetate, and the mixture is separated The organic layer is washed with a saturated brine dried over magnesium sulfate concentrated under reduced pressure

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

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

Procedure: The solution of (2-aminopyridin-3-yl)methanol (1.0 g) in THF (dry) (10 mL) was added dropwise to a solution of thionyl chloride (0.736 mL) in THF (dry) (30 mL) at 0° C. The mixture was stirred at room temperature for 30 min and concentrated in vacuo to give 3-(chloromethyl)pyridin-2-amine hydrochloride as a yellow gum. NaH (60%, 147 mg) was added to a mixture of 4-(1-methylpropyl)phenol (503 mg) in DMF (dry) (7 mL) at 0° C. The mixture was stirred at the same temperature for 20 min, then was added with the prepared 3-(chloromethyl)pyridin-2-amine hydrochloride (300 mg) at the same temperature. The mixture was stirred at 0° C. for 20 min, room temperature for 1 hr and 60° C. for 1 hr. Silica-gel was added to the mixture and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with EtOAc in hexane) to give the title compound (151 mg) as pale yellow crystals. The mixture was stirred at 0° C. for 20 min, room temperature for 1 hr and 60° C. for 1 hr Silica-gel was added to the mixture the volatiles were removed in vacuo was purified by column chromatography (silica gel, eluted with EtOAc in hexane)

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

Procedure: The solution of (2-aminopyridin-3-yl)methanol (1.0 g) in THF (dry) (10 mL) was added dropwise to a solution of thionyl chloride (0.736 mL) in THF (dry) (30 mL) at 0° C. The mixture was stirred at room temperature for 30 min and concentrated in vacuo to give 3-(chloromethyl)pyridin-2-amine hydrochloride as a yellow gum. NaH (60%, 147 mg) was added to a mixture of 4-(1-methylpropyl)phenol (503 mg) in DMF (dry) (7 mL) at 0° C. The mixture was stirred at the same temperature for 20 min, then was added with the prepared 3-(chloromethyl)pyridin-2-amine hydrochloride (300 mg) at the same temperature. The mixture was stirred at 0° C. for 20 min, room temperature for 1 hr and 60° C. for 1 hr. Silica-gel was added to the mixture and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with EtOAc in hexane) to give the title compound (151 mg) as pale yellow crystals. The mixture was stirred at 0° C. for 20 min, room temperature for 1 hr and 60° C. for 1 hr Silica-gel was added to the mixture the volatiles were removed in vacuo was purified by column chromatography (silica gel, eluted with EtOAc in hexane)

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

Procedure: To a stirred mixture of 50 ml of water, 50 ml of ether and 10.0 g of 4-sec-butylphenol was added dropwise, 7.5 ml of 61% nitric acid was added dropwise while cooling with ice. After, the temperature of the mixture was raised to room temperature and the reaction was continued for 4 days. The reaction mixture was extracted with 300 ml of ethyl acetate, washed with a brine and dried with anhydrous sodium sulfate. The drying agent was filtered off and the solvent was distilled away. The residue was purified by subjecting to silica-gel column-chromatography [eluent:chloroform] to give 14.71 g of 4-sec-butyl-2-nitrophenol. was added dropwise while cooling with ice The reaction mixture was extracted with 300 ml of ethyl acetate washed with a brine dried with anhydrous sodium sulfate The drying agent was filtered off the solvent was distilled away The residue was purified

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

Procedure: The solution of (2-aminopyridin-3-yl)methanol (1.0 g) in THF (dry) (10 mL) was added dropwise to a solution of thionyl chloride (0.736 mL) in THF (dry) (30 mL) at 0° C. The mixture was stirred at room temperature for 30 min and concentrated in vacuo to give 3-(chloromethyl)pyridin-2-amine hydrochloride as a yellow gum. NaH (60%, 147 mg) was added to a mixture of 4-(1-methylpropyl)phenol (503 mg) in DMF (dry) (7 mL) at 0° C. The mixture was stirred at the same temperature for 20 min, then was added with the prepared 3-(chloromethyl)pyridin-2-amine hydrochloride (300 mg) at the same temperature. The mixture was stirred at 0° C. for 20 min, room temperature for 1 hr and 60° C. for 1 hr. Silica-gel was added to the mixture and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with EtOAc in hexane) to give the title compound (151 mg) as pale yellow crystals. The mixture was stirred at 0° C. for 20 min, room temperature for 1 hr and 60° C. for 1 hr Silica-gel was added to the mixture the volatiles were removed in vacuo was purified by column chromatography (silica gel, eluted with EtOAc in hexane)

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

Procedure: The solution of (2-aminopyridin-3-yl)methanol (1.0 g) in THF (dry) (10 mL) was added dropwise to a solution of thionyl chloride (0.736 mL) in THF (dry) (30 mL) at 0° C. The mixture was stirred at room temperature for 30 min and concentrated in vacuo to give 3-(chloromethyl)pyridin-2-amine hydrochloride as a yellow gum. NaH (60%, 147 mg) was added to a mixture of 4-(1-methylpropyl)phenol (503 mg) in DMF (dry) (7 mL) at 0° C. The mixture was stirred at the same temperature for 20 min, then was added with the prepared 3-(chloromethyl)pyridin-2-amine hydrochloride (300 mg) at the same temperature. The mixture was stirred at 0° C. for 20 min, room temperature for 1 hr and 60° C. for 1 hr. Silica-gel was added to the mixture and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with EtOAc in hexane) to give the title compound (151 mg) as pale yellow crystals. The mixture was stirred at 0° C. for 20 min, room temperature for 1 hr and 60° C. for 1 hr Silica-gel was added to the mixture the volatiles were removed in vacuo was purified by column chromatography (silica gel, eluted with EtOAc in hexane)

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

Procedure: N-(isoquinolin-5-yl)-2-bromodecanoic amide, prepared according to the procedures described in Example 3 and 25, was coupled with 4-(1-methylpropyl)phenol according to the procedure described in Example 6 to give the title compound.

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

Procedure: By use of the procedures described in Examples 1 and 3, ethyl 2-bromononanoate and 4-(1-methylpropyl )phenol were coupled and the product saponified to give 2- (4-(1-methylpropyl)phenoxy)nonanoic acid. This material (1.0 g) was then methylated at the 2-position according to the procedure of Pfeffer, et. al. (J. Org. Chem., 1972, 37, 451) to give 2-methyl-2-hexanethiodecanoic acid (0.928 g). This material (0.86 g) was converted to the corresponding acid chloride with oxalyl chloride and coupled with 2,4,6-trimethoxyaniline (0.49 g) according to the procedure of Adams and Ulrich (J. Am. Chem. Soc., 1920, 42, 599) to give the title compound (1.12 g).

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

Procedure: By use of the procedures described in Examples 1 and 3, ethyl 2-bromononanoate and 4-(1-methylpropyl )phenol were coupled and the product saponified to give 2- (4-(1-methylpropyl)phenoxy)nonanoic acid. This material (1.0 g) was then methylated at the 2-position according to the procedure of Pfeffer, et. al. (J. Org. Chem., 1972, 37, 451) to give 2-methyl-2-hexanethiodecanoic acid (0.928 g). This material (0.86 g) was converted to the corresponding acid chloride with oxalyl chloride and coupled with 2,4,6-trimethoxyaniline (0.49 g) according to the procedure of Adams and Ulrich (J. Am. Chem. Soc., 1920, 42, 599) to give the title compound (1.12 g).