ChemicalBook CAS DataBase List ROTIGOTINE

ROTIGOTINE synthesis

11synthesis methods

Product Name:ROTIGOTINE
CAS Number:99755-59-6
Molecular formula:C19H25NOS
Molecular Weight:315.47

Rotigotine is a non-selective dopamine receptor agonist with preference for D3 receptors over D2 and D1. As such, it is an effective anti-Parkinsonian agent. Racemic rotigotine is about 50 times as potent as quinpirole, the gold standard D2 agonist.

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

ROUTE 6

ROUTE 7

ROUTE 8

ROUTE 9

ROUTE 10

Webster, Robert; Boyer, Alistair; Fleming, Matthew J.; Lautens, Mark. Practical Asymmetric Synthesis of Bioactive Aminotetralins from a Racemic Precursor Using a Regiodivergent Resolution. Organic Letters. Volume 12. Issue 23. Pages 5418-5421. 2010.

(6S)-6-(propyl-(2-thiophen-2-ylethyl)amino)tetralin-1-ol hydrochloride

125572-93-2
176 suppliers
$35.00/5mg

99755-59-6
284 suppliers
$25.00/1mg

Yield:99755-59-6 98%

Reaction Conditions:

with sodium carbonate in dichloromethane;water

Steps:

13
Example 13 Dissociation of Rotigotine hydrochloride To a 10L four-necked reaction flask equipped with a mechanical agitator and a constant pressure dropping funnel, the above prepared 363g purified rotigotine hydrochloride and dichloromethane (5475mL) were added, and neutralized by dropwise addition of 5% aqueous sodium carbonate solution. The organic phase was separated out and washed with water once and concentrated to dryness to give 320g oil. Hexane (600mL) was added to the residue to precipitate a solid, which was filtered and dried to give rotigotine solid. Chemical Purity: 99.82%, Optical Purity: 100%, Yield: 98%. ¹H-NMR(400MHz, CDCl₃):δ 7.12(m, 1H, aromatic), 7.0(m, 1H, aromatic), 6.9(m, 1H, aromatic), 6.8(m, 1H, aromatic), 6.7(m, 1H, aromatic), 6.6(m, 1H, aromatic), 4.9(broad double, 1H, -OH), 2.8(m, 8H, -CH₂-, -CH-), 2.6 (m, 3H, -CH₂-), 2.10(m, 1H, -CH₂-), 1.5(m, 3H, -CH₂-), 0.9 (t, 3H, -CH₃).

References:

2y-Chem, Ltd. EP2476676, 2012, A1 Location in patent:Page/Page column 9

FullText