1156461-19-6

Basic information

• Product Name: (R)-N,N-dimethyl-N-[3-hydroxy-3-(2-thienyl)propyl]-ammonium (S)-mandelate
• CAS NO: 1156461-19-6
• Molecular Weight: 337.44
• Mol File: 1156461-19-6.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: (R)-N,N-dimethyl-N-[3-hydroxy-3-(2-thienyl)propyl]-ammonium (S)-mandelate(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-N,N-dimethyl-N-[3-hydroxy-3-(2-thienyl)propyl]-ammonium (S)-mandelate(1156461-19-6)
• EPA Substance Registry System: (R)-N,N-dimethyl-N-[3-hydroxy-3-(2-thienyl)propyl]-ammonium (S)-mandelate(1156461-19-6)

Safety Data

• Hazardous Substances Data: 1156461-19-6(Hazardous Substances Data)

Upstream product

• 34772-98-0 3-dimethylamino-1-thiophen-2-ylpropenone 
• 132335-49-0 α-[2-(dimethylamino)ethyl](thiophene-2-yl)methanol 
• 88-15-3 2-Acetylthiophene 
• 13636-01-6 3-(dimethylamino)-1-(2-thienyl)-1-propanol hydrochloride 
• 17199-29-0 (S)-Mandelic acid 
• 13636-02-7 3-(N,N-dimethylamino)-1-(thien-2-yl)propan-1-ol 

Relevant articles and documents

Preparation method of (S)-3-N,N-disubstituted amino-1-(2-thienyl)-1-propanol

The invention discloses a preparation method of (S)-3-N,N-disubstituted amino-1-(2-thienyl)-1-propanol shown as the formula (I). The method comprises: taking 2-acetyl thiophene shown in the formula (II) as a raw material, and allowing 2-acetyl thiophene to completely react with di(trichloromethyl)carbonic ester (III) and N,N-disubstituted methanamide (IV) in an organic solvent under the catalysis of an organic base to obtain N,N-disubstituted amino-1-(2-thienyl)-1-acrylketone shown as the formula (V); and performing hydrogenation reduction with lithium aluminium hydride to obtain N,N-disubstituted amino-1-(2-thienyl)-1-propanol shown as the formula (VI); and performing splitting with S-mandelic acid and recrystallization with ethyl acetate to obtain the target product shown as the formula (I). The preparation method is low in cost, mild in reaction condition, less in waste water, waste gas and industrial residue, small in energy consumption, and high in yield. The preparation method is safe and is suitable for industrial production.

Synthesis of (S)-3-(N-methylamino)-1-(2-thienyl)propan-1-ol: Revisiting Eli Lilly's resolution-racemization-recycle synthesis of duloxetine for its robust processes

(±)-3-(N,N-Dimethylamino)-1-(2-thienyl)propan-1-ol (6), prepared from 2-acetylthiophene (4) in a two-step overall yield of 79%, is resolved into (S)-6 of 93% ee as its diastereomeric salt (8) with (S)-mandetic acid (7) according to Eli Lilly's procedures developed for the resolution-racemization- recycle (RRR) synthesis of duloxetine (2) with some modifications in terms of practicality. On its liberation from 8, (S)-6 undergoes N-demethylative ethyl carbamate formation in two discrete but successive steps in an overall yield of 87% from 8: (1) O-ethyl carbonate formation and (2) ethyl carbamate formation with concomitant loss of the N-methyl group. Alkaline hydrolysis then affords (S)-3-(N-methylamino)-1-(2-thienyl)propan-1-ol (1) of 100% ee, an alleged penultimate precursor to duloxetine (2), in 75% yield after a single recrystallization from ethylcyclohexane. In the overall process thus developed, PhMe is substituted successfully for t-BuOMe, a solvent that has been used favorably in Eli Lilly's original RRR synthesis of 2.