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(S)-2-methoxy-5-([1-(4-phenyl-1H-imidazol-2-yl)ethylamino]methyl)benzoic acid methyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93.2 g
(S)-1-(4-phenyl-IH-imidazol-2-yl)ethanamine (48.2 gms) was added to a mixture of <strong>[78515-16-9]methyl-5-formyl-2-methoxybenzoate</strong> (50 gms) and methanol (300 ml) at 25-30°C and stirred for 2 hours at the same temperature. Cooled the reaction mixture to 0-5°C. Sodium borohydride (12.6 gms) was added to the reaction mixture at 0-5°C and stirred for 4 hours at the same temperature. Water (250 ml) was slowly added to the reaction mixture at 0-5°C. pHreaction mixture was adjusted to 2.0 using aqueous hydrochloric acid solution (75 ml) at 0- 5°C. Ethyl acetate (250 ml) was added to the reaction mixture at 0-5°C. Basified the reaction mixture using 10percent sodium hydroxide solution at 0-5°C. Raised the reaction temperature to 25-30°C and stirred for 30 minutes at the same temperature. Both the organic and aqueous layers were separated and aqueous layer was extracted with ethyl acetate. Combine the organic layer and washed with aqueous sodium chloride soLution. Distilled off the solvent completely from the organic layer under reduced pressure. Isopropanol (250 ml) was added to the obtained residue at 25-30°C and stirred for 10 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture under reduced pressure to get the title compound. Yield: 93.2 gms; Purity by HPLC: 9 1.16percent.
40 g
With sodium tetrahydroborate; acetic acid; In methanol; at 5 - 20℃;
To a stirred solution of l-(4-phenyl-1H-imidazole-2-yl)-ethyl amine (20 gm) and <strong>[78515-16-9]5-formyl-2-methoxy-benzoic acid methyl ester</strong> (20 gm) in methanol was added catalytic amount of acetic acid (3 ml). The reaction mixture was cooled at 5°C-l0°C and sodiumborohydride (4 gm) was added. The reaction mixture was further stirred for 2-3 hours at room temperature. The resultant mixture was diluted with water and then partially concentrated. To this mixture was added 2N HC1 solution followed by addition of dichloromethane. The phases were separated and the pH (9-11) of aqueous layer was adjusted using 2N NaOH solution; which was further extracted with dichloromethane.The combined organic layers were concentrated under vacuum to afford titled compound as oil (yield: 40 gm).
Benzyl [(lS)-l-(4-phenyl-lH-imidazol-2-yl)ethyl]carbamate (25 g; Formula Ila or Formula II, when PG is benzyloxycarbonyl) was added to methanol (125 mL) at room temperature to obtain a mixture. Palladium on carbon (Pd/C) (2.5percent; 50percent wet; 3.75 g) was added to the mixture at room temperature. Hydrogen pressure (3 kg/cm2 to 4 kg/cm2) was applied to the reaction mass and then stirred for 4 hours at room temperature. The reaction mixture was filtered through Hyflo® bed and then washed with methanol (50 mL) to obtain a filtrate. (0278) Methyl 5-formyl-2-methoxybenzoate (16.54 g; Formula IVa or IV, when R is methyl) was added to the filtrate at room temperature to obtain a reaction mixture. The reaction mixture was stirred for one hour at room temperature and then cooled to 0°C. (0279) Sodium borohydride (4.39 g) was added in lots to the reaction mixture and then stirred for 4 hours at 0°C to 10°C. Sodium borohydride (1.1 g) was again added in lots at 0°C to 10°C and then stirred for 2 hours at 0°C to 10°C. Water (75 mL) and dichloromethane (105 mL) were added to the reaction mixture at 0°C to 10°C and then stirred for 10 minutes. The layers were separated and the organic layer was washed with 5percent sodium bicarbonate (75 mL) at 0°C to 10°C. The aqueous layer was extracted with (0280) dichloromethane (45 mL) at 0°C to 10°C. The combined organic layers were recovered under vacuum at 45°C to obtain the title compound. (0281) Yield: 28.22 g (0282) Chromatographic purity: 74.1percent
With methanol; sodium tetrahydroborate; acetic acid; at -10 - 30℃;
To a stirred solution of 1-(4-phenyl-1H-imidazole-2-yl)ethylamine (95 gm) and <strong>[78515-16-9]5-formyl-2-methoxy-benzoic acid methyl ester</strong> (100 gm) in methanol (250 ml) was added catalytic amount of acetic acid (1 ml). The reaction mixture was cooled at -10 to 10°C and sodium borohydride (9.7 gm) was added. The reaction mixture was further stirred for 2-3 hours at room temperature. The resultant mixture was diluted with water and dichloromethane. The organic phases were separated and further partially concentrated under vacuum to obtain 2-methoxy-5-[l-(4-phenyl-lH-imidazol-2-yl)ethylamino]- methyl)benzoic acid methyl ester; which was further added into the mixture of 2-tert- butoxycarbonylamino-3-(4-carbamoyl-2,6-dimethyl-phenyl-propionic acid (138 gm), 1- ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HC1, 277 gm) and 1- hydroxybenzotriazole (HOBt, 78.8 gm) in dimethylformamide (400 ml). Diisopropylethylamine (DIPEA) was further added and resultant mixture was further stirred for 3 to 4 hours at room temperature. The resultant mixture was diluted with water and dichloromethane. The separated organic phase was washed sequentially with aqueous NaOH solution, 10percent HCl solution and water. The reaction mixture was cooled, filtered and further purified using methanol and ethyl acetate to afford titled compound (yield: 185 gm).
methyl 2-methoxy-5-([(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]amino}methyl)benzoate citrate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
10.3 g
Method C: Benzyl [(15)-l-(4-phenyl-lH-imidazol-2-yl)ethyl]carbamate (10 g; Formula Ila or Formula II, when PG is benzyloxycarbonyl) was added to methanol (50 mL) at room temperature. Palladium on carbon (2.5percent, 50percent wet; 4 g) was added at room temperature. Hydrogen pressure (3.0 kg/cm2 to 4.0 kg/cm2) was applied to the reaction mass and then stirred for 2 hours at 30°C. Methyl 5-formyl-2-methoxybenzoate (5.7 g; Formula IVa or IV, when R is methyl) was added to the mixture at room temperature and hydrogen pressure (3.0 kg/cm2 to 4.0 kg/cm2) was applied. The reaction mixture was stirred for 4 hours at 30°C. The reaction mixture was filtered through Hyflo® bed and then washed with methanol (20 mL) to obtain a filtrate. An aqueous solution of citric acid (50percent, 14 mL) was added to the filtrate at room temperature to obtain a reaction mass. The reaction mass was stirred for 2 hours at 20°C to 22°C. The solid so obtained was filtered, washed with water (50 mL), suck dried and then dried overnight in air oven at 60°C to 65°C to obtain the title compound. (0295) Yield: 10.3 g (0296) Chromatographic purity: 98.97percent
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