ChemicalBook CAS DataBase List TETRABENAZINE

TETRABENAZINE synthesis

6synthesis methods

Product Name:TETRABENAZINE
CAS Number:718635-93-9
Molecular formula:C19H27NO3
Molecular Weight:317.42

3-(N,N-Dimethylaminomethyl)-5-methyl-2-hexanone

91342-74-4

6,7-Dimethoxy-3,4-dihydroisoquinoline hydrochloride

20232-39-7

718635-93-9

6,7-Dimethoxy-3,4-dihydroisoquinoline hydrochloride (118.2 kg) was dissolved in water (3 volumes). A solution of 3-((dimethylamino)methyl)-5-methylhexan-2-one (99.1 kg) in n-heptane (1.5 vol) was added, and the reaction mixture was stirred vigorously at 35 °C for at least 48 hours until the amount of 6,7-dimethoxy-3,4-dihydroisoquinoline was reduced to less than 10% of the initial amount (as detected by a standard solution). After completion of the reaction, the solid product was collected by filtration, washed sequentially with water and n-heptane, and then dried under vacuum to afford 3-isobutyl-9,10-dimethoxy-3,4,6,7-tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one (141.1 kg, 85.6% yield).

91342-74-4
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$15.00/1g

20232-39-7
252 suppliers
$10.00/1g

718635-93-9
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Yield:718635-93-9 85.6%

Reaction Conditions:

in n-heptane;water at 35; for 48 h;Large scale;

Steps:

1.A1 A1. Preparation of 3-isobutyl-9,10-dimethoxy-3,4,6,7-tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one starting from 3-((dimethylamino)methyl)-5-methylhexan-2-one free base
6,7-dimethoxy-3,4-dihydroisoquinoline hydrochloride (118.2 kg) was dissolved in water (3 volumes). 34(Dimethylamino)methyl)-5-methylhexan-2-one (99.1 kg) in n-heptane (1.5 volumes) was added and the mixture stirred vigorously for at least 48 hours at about 35° C. until less than 10% 6,7-dimethoxy-3,4-dihydroisoquinoline was remaining against a standard solution. The solid was filtered, washed with water then heptane, and then dried under vacuum to provide 3-isobutyl-9,10-dimethoxy-3,4,6,7-tetrahydro-1H-pyrido[2,1-a]isoquinolin-2(11bH)-one (141.1 kg, 85.6% yield).

References:

Neurocrine Biosciences, Inc.;MCGEE, Kevin;LI, Bin-Feng US2017/183346, 2017, A1 Location in patent:Paragraph 0165

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