ChemicalBook CAS DataBase List Ranolazine

Ranolazine synthesis

10synthesis methods

Product Name:Ranolazine
CAS Number:95635-55-5
Molecular formula:C24H33N3O4
Molecular Weight:427.54

Two syntheses, one from the inventors at Roche and other from a group in Hungary, of Ranolazine have been described in the patent literature. The original synthesis is highlighted in the Scheme. Reaction of 2,6-dimethylaniline 46 with chloroacetyl chloride (47) in the presence of triethylamine for 4h at 0oC gave amide 48 in 82% yield. This chloro amide 48 was reacted with piperazine in refluxing ethanol for 2 h to give piperazinyl amide 50. Reaction of amide 50 with epoxide intermediate 53, prepared by reacting 2-methoxy phenol 51 with epichlorohydrin, in refluxing isopropanol for 3 h followed by treatment with HCl/methanol gave ranolazine dihydrochloride (VII) in 73% yield.

2210-74-4 Synthesis

2210-74-4
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$6.00/250mg

N-(2,6-Diphenylmethyl)-1-piperazine acetylamine

5294-61-1
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$28.00/5g

95635-55-5
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$5.00/100mg

Yield:95635-55-5 85%

Reaction Conditions:

with Sulfated tungstate at 70; for 2 h;Green chemistry;

Steps:

General procedure for epoxide opening reaction

General procedure: Sulfated tungstate (10 wt%) was added to a solution of cyclohexene oxide (1 g, 10.18 mmol) and aniline (0.95 g, 10.18 mmol) in solvent-free condition and the mixture was stirred at room temperature. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with ethyl acetate (15 ml) and filtered to recover the catalyst. Organic layer washed with water (10 ml), dried over Na₂SO₄ and concentrated under reduced pressure to give the crude product which was purified by chromatography on silica gel (60-120) with hexane-ethyl acetate (8:2) as eluent to get pure 2-(phenylamino) cyclohexanol as a white solid.

References:

Pathare, Sagar P.;Akamanchi, Krishnacharya G. [Tetrahedron Letters,2013,vol. 54,# 48,p. 6455 - 6459]