ChemicalBook CAS DataBase List Clopidogrel hydrogen sulfate

Clopidogrel hydrogen sulfate synthesis

4synthesis methods

Product Name:Clopidogrel hydrogen sulfate
CAS Number:135046-48-9
Molecular formula:C16H18ClNO6S2
Molecular Weight:419.89

28783-41-7 Synthesis

4,5,6,7-Tetrahydrothieno[3,2,c] pyridine hydrochloride

28783-41-7
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$5.00/5g

85259-19-4 Synthesis

Methyl alpha-bromo-2-chlorophenylacetate

85259-19-4
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$12.00/25g

135046-48-9
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$35.00/50mg

Yield:135046-48-9 90%

Reaction Conditions:

Stage #1:6,7-dihydro-4H-thieno[3,2-c]pyridine hydrochloride with sodium carbonate in water at 25; for 0.5 h;
Stage #2:methyl 2-bromo-2-(2-chlorophenyl)acetate in water;toluene at 20; for 12 h;
Stage #3: with sulfuric acid in ethyl acetate for 1 h;Reagent/catalyst;Solvent;

Steps:

One-Pot Procedure for the Synthesis of Racemic ClopidogrelBisulfate (2)
To a vessel equipped with Dean-Stark assembly, 2-(thiophen-2-yl)ethanamine 5 (0.48 g, 4 mmol), PFA (0.13 g,4.3 mmol), and toluene (6 mL) were added and the reaction mixture was refluxed for 2 h to obtain a yellow solution contain imine. After cooling to 20C, a solution of6N HCl (0.7 mL) in DMF was added into the reactionmixture and continued to heat at 50C for 1 h to produce 4as a white precipitate. The reaction was cooled to 25Cand aqueous solution of 10% Na2CO3 was added andstirred for 30 min. Then a solution of methyl-2-bromo-2-(2-chlorophenyl)acetate 3 (1.04 g, 4 mmol) in toluene (7mL) was added to the reaction mixture. The reaction mixture stirred at room temperature for 12 h. The aqueouslayerisdiscardedandtheorganiclayerwaswashedwithwater. The organic phase was evaporated, to afford viscose oil. To this oil, conc. H2SO4 (0.42 mL) and EtOAc(8 mL) was added. The mixture was stirred for 1 h. Theprecipitated crystalsfiltered off and washed with cool acetone. The pure racemic clopidogrel bisulfate 2was driedin oven at 50C (1.35 g, 90% yield). White powder; mp220-222C; IR:v (KBr, cm-1) 3434 (OH stretch), 3100,2989, 2953, 1755 (C DO stretch), 1239, 1222 (C-Ostretch), 1063.

References:

Mahmoodi, Nosrat O.;Ghavidast, Atefeh;Ashkan, Mitra;Mamaghani, Manouchehr;Zanjanchi, Mohammad Ali;Tabatabaeian, Khalil;Arabanian, Armin [Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry,2016,vol. 46,# 10,p. 1552 - 1557]

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