ChemicalBook CAS DataBase List 5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester

5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester synthesis

13synthesis methods

Product Name:5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester
CAS Number:3543-74-6
Molecular formula:C18H27N3O4
Molecular Weight:349.42

Stir and dissolve 5-amino-1-methyl-1H-2-benzimidazole butyric acid ethyl ester (60g, 0.23mol), 600mL water, and 300mL glacial acetic acid in a 2L reaction flask, and cool to -50, Add 120 mL of ethylene oxide, and control the temperature to complete the reaction. Adjust the pH of the potassium carbonate solution to 7.0-7.3, extract with dichloromethane 300 mL×3, combine the organic phases, wash with purified water 200 mL×3, dry with anhydrous magnesium sulfate, filter, and concentrate to obtain a brown solid. Then add 1200 mL of ethyl acetate and heat to 70-80° C. to dissolve, cool to room temperature to crystallize, filter and dry to obtain 63 g of light brown solid 5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester with a purity of 99.3%. The yield was 78.5%.

5-[Bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazole-2-butanoic acid ethyl ester

75-21-8
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3543-73-5 Synthesis

1-Methyl-5-amino-1H-benzimidazole-2-butanoic acid ethyl ester

3543-73-5
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3543-74-6
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$25.00/250mg

Yield:3543-74-6 78.53%

Reaction Conditions:

Stage #1:oxirane;ethyl 4‐(5‐amino‐1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)butanoate with sodium acetate trihydrate in water;acetic acid at 0 - 25; for 23 h;
Stage #2: with potassium carbonate in dichloromethane at 20 - 25;

Steps:

5 Preparation of Ethyl 4-{5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl}butanoate (III)
Example-5
Preparation of Ethyl 4-{5-[bis(2-hydroxyethyl)amino]-1-methyl-1H-benzimidazol-2-yl}butanoate (III)
Ethyl 4-[5-amino-1-methyl-1H-benzimidazol-2-yl)butanoate (II, 200.0 g, 0.763 mol) was added to DM Water (1.1 L).
Aqueous sodium acetate.3H₂O (20.0 g sodium acetate.3H₂O in 100 mL DM water) and acetic acid (400 mL) was added and agitated till complete dissolution of compound of the formula II.
The reaction mixture was cooled to 0-5° C. and ethylene oxide (270.0 g, 6.12 mole) was added maintaining the temperature of the reaction mixture at 0-5° C.
The reaction mixture was stirred at 0-5° C. for 5 hours.
The temperature of reaction mixture was raised to 20-25° C. and agitated at 20-25° C. for 18 hours.
After completion of the reaction, dichloromethane (2.0 L) was added at 20-25° C. followed by addition of aqueous solution of potassium carbonate (440.0 g potassium carbonate in 1.1 L DM water) portion wise at 20-25° C. to control the evaluation of effervescence and agitated at 20-25° C. for 5-10 minutes.
The layers were separated.
The organic layer (dichloromethane) was washed with DM water (1.0 L) twice and organic layer was concentrated under vacuum at 40-50° C. till viscous mass is obtained.
The viscous mass was dissolved in acetone (1.0 L), cooled to 0-5° C. and agitated at 0-5° C. for 1 hour.
The solid separated out was filtered, washed with chilled (0-5° C.) acetone (200.0 mL) and dried at 40-50° C. under vacuum for 6 hours to give the title compound (III, 210.0 g; 78.53%), with a purity of 99.06%.

References:

FRESENIUS KABI ONCOLOGY LIMITED;MISHRA, Bhuwan Bhaskar;KACHHADIA, Nikunj Shambhubhai;TOMAR, Vinod Singh;LAHIRI, Saswata US2014/121383, 2014, A1 Location in patent:Paragraph 0094

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3543-73-5 Synthesis

3543-73-5
206 suppliers
$7.00/250mg