1,4-dimethoxynaphthalene

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

Conditions: temp:66.01; pressure:0.00; stir:

Conditions: temp:66.01; pressure:0.00; stir:

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

Procedure: To a solution of 50 grams (0.26 mol) of 1,4-dimethoxynaphthalene, prepared according to the procedure of L. Fieser, in the Journal of the American Chemical Society, Volume 70, page 3165 (1948), in 500 ml glacial acetic acid is added 13.7 ml (0.26 mol) of bromine at room temperature. The mixture is stirred for 1 hour, and the solvent is removed under reduced pressure and the residue dissolved in ether. The resulting solution is carefully washed twice with sodium bicarbonate, the organic layer separated, dried over sodium sulfate and the solvent removed. Distillation of the residue gave 63.4 grams (81% of theoretical yield) of liquid 2-bromo-1,4-dimethoxy-naphthalene (boiling 200°-210° at 0.1 mm Hg). The product has a nuclear magnetic resonance spectrum consistant with the expected structure and has peaks expressed in parts per million relative to tetramethylsilane at 8.0 (m,2H), 7.4(m,2H), 6.9(s,1H), 3.9(d,6H). the solvent is removed under reduced pressure the residue dissolved in ether The resulting solution is carefully washed twice with sodium bicarbonate the organic layer separated dried over sodium sulfate the solvent removed Distillation of the residue gave

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

Procedure: To a solution of 50 grams (0.26 mol) of 1,4-dimethoxynaphthalene, prepared according to the procedure of L. Fieser, in the Journal of the American Chemical Society, Volume 70, page 3165 (1948), in 500 ml glacial acetic acid is added 13.7 ml (0.26 mol) of bromine at room temperature. The mixture is stirred for 1 hour, and the solvent is removed under reduced pressure and the residue dissolved in ether. The resulting solution is carefully washed twice with sodium bicarbonate, the organic layer separated, dried over sodium sulfate and the solvent removed. Distillation of the residue gave 63.4 grams (81% of theoretical yield) of liquid 2-bromo-1,4-dimethoxy-naphthalene (boiling 200°-210° at 0.1 mm Hg). The product has a nuclear magnetic resonance spectrum consistant with the expected structure and has peaks expressed in parts per million relative to tetramethylsilane at 8.0 (m,2H), 7.4(m,2H), 6.9(s,1H), 3.9(d,6H). the solvent is removed under reduced pressure the residue dissolved in ether The resulting solution is carefully washed twice with sodium bicarbonate the organic layer separated dried over sodium sulfate the solvent removed Distillation of the residue gave

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

Procedure: The process of preparing the novel compounds of this invention comprises the steps of (1) brominating 1,4-dimethoxynaphthalene with liquid bromine in an organic solvent such as acetic acid at room temperature to form the 2-bromo-1,4-dimethoxynaphthalene, (2) converting the bromine derivative to the carboxylic acid derivative by lithiation and carboxylation. The lithiation is conducted in a known procedure, as for example, by treating the bromo derivative with n-Butyllithium in an organic solvent under anhydrous conditions at a low temperature, such as -78° C. The resulting lithium compound is not isolated, but converted into the carboxylic acid by adding dry ice to the cooled lithium compound and allowing the reaction mixture to come to room temperature. (3) The carboxylic acid derivative is then converted to the acid chloride by treating with thionyl chloride at room temperature. (4) The resulting acid chloride is condensed with the appropriate amine to form the carboxamide. The condensation reaction is carried out by treating the acid chloride in an organic solvent with the appropriate amine at room temperature in the presence of a proton acceptor. The process of preparing the novel compounds of this invention at room temperature

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

Procedure: The process of preparing the novel compounds of this invention comprises the steps of (1) brominating 1,4-dimethoxynaphthalene with liquid bromine in an organic solvent such as acetic acid at room temperature to form the 2-bromo-1,4-dimethoxynaphthalene, (2) converting the bromine derivative to the carboxylic acid derivative by lithiation and carboxylation. The lithiation is conducted in a known procedure, as for example, by treating the bromo derivative with n-Butyllithium in an organic solvent under anhydrous conditions at a low temperature, such as -78° C. The resulting lithium compound is not isolated, but converted into the carboxylic acid by adding dry ice to the cooled lithium compound and allowing the reaction mixture to come to room temperature. (3) The carboxylic acid derivative is then converted to the acid chloride by treating with thionyl chloride at room temperature. (4) The resulting acid chloride is condensed with the appropriate amine to form the carboxamide. The condensation reaction is carried out by treating the acid chloride in an organic solvent with the appropriate amine at room temperature in the presence of a proton acceptor. The process of preparing the novel compounds of this invention at room temperature

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

Procedure: To a solution of 50 grams (0.26 mol) of 1,4-dimethoxynaphthalene, prepared according to the procedure of L. Fieser, in the Journal of the American Chemical Society, Volume 70, page 3165 (1948), in 500 ml glacial acetic acid is added 13.7 ml (0.26 mol) of bromine at room temperature. The mixture is stirred for 1 hour, and the solvent is removed under reduced pressure and the residue dissolved in ether. The resulting solution is carefully washed twice with sodium bicarbonate, the organic layer separated, dried over sodium sulfate and the solvent removed. Distillation of the residue gave 63.4 grams (81% of theoretical yield) of liquid 2-bromo-1,4-dimethoxy-naphthalene (boiling 200°-210° at 0.1 mm Hg). The product has a nuclear magnetic resonance spectrum consistant with the expected structure and has peaks expressed in parts per million relative to tetramethylsilane at 8.0 (m,2H), 7.4(m,2H), 6.9(s,1H), 3.9(d,6H). the solvent is removed under reduced pressure the residue dissolved in ether The resulting solution is carefully washed twice with sodium bicarbonate the organic layer separated dried over sodium sulfate the solvent removed Distillation of the residue gave

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

Procedure: The process of preparing the novel compounds of this invention comprises the steps of (1) brominating 1,4-dimethoxynaphthalene with liquid bromine in an organic solvent such as acetic acid at room temperature to form the 2-bromo-1,4-dimethoxynaphthalene, (2) converting the bromine derivative to the carboxylic acid derivative by lithiation and carboxylation. The lithiation is conducted in a known procedure, as for example, by treating the bromo derivative with n-Butyllithium in an organic solvent under anhydrous conditions at a low temperature, such as -78° C. The resulting lithium compound is not isolated, but converted into the carboxylic acid by adding dry ice to the cooled lithium compound and allowing the reaction mixture to come to room temperature. (3) The carboxylic acid derivative is then converted to the acid chloride by treating with thionyl chloride at room temperature. (4) The resulting acid chloride is condensed with the appropriate amine to form the carboxamide. The condensation reaction is carried out by treating the acid chloride in an organic solvent with the appropriate amine at room temperature in the presence of a proton acceptor. The process of preparing the novel compounds of this invention at room temperature

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

Procedure: To a suspension of AlCl3 (3.8 g, 28.6 mmol) in dichloromethane (100 mL) was added a solution of 1,4-dimethoxynaphthalene (4.88 g, 25.9 mmol) in dichloromethane (50 mL). To this mixture was added a solution of (R)-N-trifluoroacetylalanine (16 g, 86.5 mmol) in CH2Cl2 (50 mL); this mixture was stirred at room temperature for 3 h. The reaction mixture was poured slowly into ice (200 g) to quench the reaction and the organic layer was separated and dried (MgSO4). The solvent was evaporated and the residue was purified by flash chromatography (silica gel, ethyl acetate/hexane: 1/9) to give a yellow oil (3 g): 1H NMR (DMSO-d6) δ 1.24 (d, 3H, CH3), 3.93 (s, 3H, OCH3), 4.01 (s, 3H, OCH3), 5.51 (m, 1H), 6.99 (s, 1H, Ar—H), 7.96 (m, 2H, Ar—H), 8.17 (m, 2H, Ar—H), 9.83 (d, NH); MS 356 (M+1). to quench the reaction the organic layer was separated dried (MgSO4) The solvent was evaporated the residue was purified by flash chromatography (silica gel, ethyl acetate/hexane: 1/9)

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

Procedure: To a cold solution (ice bath) of 1,4-dimethoxy-naphthalene (5 g, 26.6 mmol) in dichloroethane (100 mL) was added propionyl chloride (2.7 g, 29.3 mmol) followed by aluminum chloride (3.9 g, 29.3 mmol). After the addition was complete, the reaction mixture was allowed to warm to room temperature and stirred for 4 hr. Water (200 mL) was added and the organic material was extracted with dichloromethane (200 mL). The organic extracts were dried (MgSO4) and concentrated to give a residue which was purified by flash chromatography (silica gel, ethyl acetate/hexane: 1/9) to give an oil (1.4 g): 1H NMR (DMSO-d6) δ 1.16 (t, 3H, CH3), 3.13 (q, 2H, CH2), 3.87 (s, 3H, OCH3), 3.98 (s, 3H, OCH3), 7.02 (s, 1H, Ar—H), 7.67 (m, 2H, Ar—H), 8.10 (d, 2H, Ar—H); MS 245 (M+1). After the addition the organic material was extracted with dichloromethane (200 mL) The organic extracts were dried (MgSO4) concentrated to give a residue which was purified by flash chromatography (silica gel, ethyl acetate/hexane: 1/9)

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

Procedure: To a solution of 1,4-dimethoxy-naphthalene (5 g, 26.6 mmol) in dichloromethane (100 mL) at 0° C. was added dichloromethyl methyl ether (3.66 g, 31.9 mmol) and stannic chloride (13.8 g, 53.1 mmol). The reaction mixture was stirred for 30 min at this temperature, allowed to warm to room temperature and stirred for an additional 30 min. Water (100 mL) was added and the mixture was extracted with dichloromethane (2×100 mL) and the combined extracts dried (MgSO4). The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, ethyl acetate/hexane: 2/8) to give a white solid: 1H NMR (DMSO-d6) δ 4.06 (s, 3H, CH3), 4.13 (s, 3H, CH3), 7.14 (s, 1H, Ar—H), 7.82 (m, 2H, Ar—H), 8.29 (m, 2H, Ar—H), 10.54 (s, 1H, CHO). stirred for an additional 30 min the mixture was extracted with dichloromethane (2×100 mL) the combined extracts dried (MgSO4) The solvent was removed under reduced pressure the residue was purified by column chromatography (silica gel, ethyl acetate/hexane: 2/8) to give a white solid