156925-17-6

Basic information

• Product Name: (+/-)-2-(chloromethyl)-4-(4-fluorobenzyl)morpholine
• Synonyms: (+/-)-2-(chloromethyl)-4-(4-fluorobenzyl)morpholine
• CAS NO: 156925-17-6
• Molecular Weight: 243.709
• Mol File: 156925-17-6.mol

Chemical Properties

• CAS DataBase Reference: (+/-)-2-(chloromethyl)-4-(4-fluorobenzyl)morpholine(CAS DataBase Reference)
• NIST Chemistry Reference: (+/-)-2-(chloromethyl)-4-(4-fluorobenzyl)morpholine(156925-17-6)
• EPA Substance Registry System: (+/-)-2-(chloromethyl)-4-(4-fluorobenzyl)morpholine(156925-17-6)

Safety Data

• Hazardous Substances Data: 156925-17-6(Hazardous Substances Data)

Upstream product

• 22116-33-2 2-(4-fluoro-benzyl-amino)-ethanol 
• 106-89-8 epichlorohydrin 
• 459-57-4 4-fluorobenzaldehyde 
• 156816-53-4 1-Chloro-3-[(4-fluoro-benzyl)-(2-hydroxy-ethyl)-amino]-propan-2-ol 

Downstream Products

• 636582-78-0 2-[4-(4-fluoro-benzyl)-morpholine-2-yl-methyl]-isoindole-1,3-dion 
• 156925-19-8 (S)-(+)-<4-(4-fluorobenzyl)-2-morpholinyl>methyl p-toluenesulfonate 
• 156925-20-1 (R)-(-)-<4-(4-fluorobenzyl)-2-morpholinyl>methyl p-toluenesulfonate 
• 156816-52-3 (+/-)-<4-(4-fluorobenzyl)-2-morpholinyl>methyl p-toluenesulfonate 
• 156816-57-8 (S)-2-Azidomethyl-4-(4-fluoro-benzyl)-morpholine 
• 156334-90-6 (R)-(+)-<4-(4-fluorobenzyl)-2-morpholinyl>methylamine 
• 156334-89-3 (S)-(-)-<4-(4-fluorobenzyl)-2-morpholinyl>methylamine 
• 156816-54-5 (+/-)-4-(4-fluorobenzyl)-2-morpholinylmethanol 

Relevant articles and documents

PROCESS FOR THE SYNTHESIS OF A BENZAMIDE DERIVATIVE

The invention relates to a process for the synthesis of mosapride citrate of formula (I), the chemical name: (R,S)-4-amino-5-chloro-2-ethoxy-N-{ [4-(4-fluoro-benzyl)-2- morpholinyl]-methyl}benzamide citrate dihydrate, (I), (II) reacting the compound of formula (II) with di-tert-butyl-dicarbonate in an alcohol in the presence of a base, the obtained product is ethylated in an inert solvent in the presence of a base, the obtained compound is hydrolyzed with an alkyl-hydroxide and the obtained salt neutralized with an acid, the obtained product is chlorinated, and the obtained compound of formula (VI) is reacted with the compound of formula (VII), (VI), (VII) where BOC is tert-butoxy-carbonyl protecting group and removing the protecting group from the obtained compound of formula (VIII) the mosapride base is prepared, (VIII) where BOC is defined as above and in desired case with an acid, preferably with citric acid a pharmaceutically acceptable salt, preferably the mosapride citrate dehydrate of formula (I) is produced.

Synthesis and biological activities of the optical isomers of (±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]me thyl]benzamide (Mosapride)

The enantiomers, (S)-(-)-1 and (R)-(+)-1, of (+)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]met hyl]benzamide (mosapride) [(+)-1], a new and selective gastroprokinetic agent, were prepared from optically active [4-(4-fluorobenzyl)-2-morpholinyl]methylamines (S)-(-)-4 and (R)-(+)-4, respectively. The requisite (S)-(-)-4 and (R)-(+)-4 were prepared by optical resolution of [4-(4-fluorobenzyl)-2-morpholinyl]methyl p-toluenesulfonate [(+)-5] using (-)- and (+)-N-(p-toluenesulfonyl)glutamic acids, followed by amination of the tosyloxy groupe of (R)-(-)-5 and (S)-(+)-5, respectively. The absolute configurations of (R)-(-)-5 and (S)-(+)-5 were determined on the basis of an asymmetric synthesis of (R)-(-)-5 from (S)-(+)-benzyl glycidyl ether [(S)-(+)-11]. Mosapride and its enantiomers, (S)-(-)-1 and (R)-(+)-1, were essentially equipotent in serotonin 5-HT4 receptor agonistic activity on the electrically evoked contractions in isolated guinea pig ileum.