(4R)-1-(Phenylmethoxy)-4-[(2,4,5-trifluorophenyl)methyl]-2-azetidinone

Base Information

• Chemical Name: (4R)-1-(Phenylmethoxy)-4-[(2,4,5-trifluorophenyl)methyl]-2-azetidinone
• CAS No.: 767352-30-7
• Molecular Formula: C17H14F3NO2
• Molecular Weight: 321.299
• Mol file: 767352-30-7.mol

Synonyms:(4R)-1-(Phenylmethoxy)-4-[(2,4,5-trifluorophenyl)methyl]-2-azetidinone;2-Azetidinone, 1-(phenylmethoxy)-4-[(2,4,5-trifluorophenyl)methyl]-, (4R)-

Chemical Property of (4R)-1-(Phenylmethoxy)-4-[(2,4,5-trifluorophenyl)methyl]-2-azetidinone

Chemical Property:

• Melting Point: 80 oC
• Boiling Point: 395.4±52.0 °C(Predicted)
• PSA: 29.54000
• Density: 1.35
• LogP: 3.31700

Purity/Quality:

99% ^*data from raw suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

Technology Process of (4R)-1-(Phenylmethoxy)-4-[(2,4,5-trifluorophenyl)methyl]-2-azetidinone

There total 10 articles about (4R)-1-(Phenylmethoxy)-4-[(2,4,5-trifluorophenyl)methyl]-2-azetidinone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 76.0%

C17H16F3NO3 → N-(benzyloxy)-4(R)-[1-methyl-(2,4,5-trifluorophenyl)]-2-oxoazetidine (767352-30-7)

Guidance literature:

With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; water; at 10 ℃; for 0.5h;

Reference yield: 76.0%

3(S)-4-(2,4,5-trifluorophenyl)-3-hydroxybutanoic acid (868071-17-4) + O-benzylhydroxylamine hydrochloride → N-(benzyloxy)-4(R)-[1-methyl-(2,4,5-trifluorophenyl)]-2-oxoazetidine (767352-30-7)

Guidance literature:

3(S)-4-(2,4,5-trifluorophenyl)-3-hydroxybutanoic acid; O-benzylhydroxylamine hydrochloride; With dicyclohexyl-carbodiimide; lithium hydroxide; In tetrahydrofuran; cis-1,2-Dichloroethylene; water; at 20 - 22 ℃; for 3h;

With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; water; at 10 - 20 ℃; for 18.5h;

Reference yield:

(2,4,5-trifluorophenyl)acetic acid (209995-38-0) → N-(benzyloxy)-4(R)-[1-methyl-(2,4,5-trifluorophenyl)]-2-oxoazetidine (767352-30-7)

Guidance literature:

Multi-step reaction with 5 steps

1.1: triethylamine / acetonitrile / 8.3 h / 30 - 50 °C

1.2: 3.5 h / 30 °C

2.1: hydrogen / dichloro[(S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl]ruthenium(II) / acetic acid; methanol / 6 h / 70 °C / 3620.13 Torr / Inert atmosphere

3.1: sodium hydroxide; methanol / water / 1.5 h / 20 - 25 °C

3.2: 2 h / 10 - 15 °C

4.1: dicyclohexyl-carbodiimide; lithium hydroxide / water; tetrahydrofuran / 3 h / 20 - 22 °C

5.1: di-isopropyl azodicarboxylate / triphenylphosphine / water; tetrahydrofuran / 0.5 h / 10 °C

With methanol; di-isopropyl azodicarboxylate; hydrogen; triethylamine; dicyclohexyl-carbodiimide; sodium hydroxide; lithium hydroxide; dichloro[(S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl]ruthenium(II); triphenylphosphine; In tetrahydrofuran; methanol; water; acetic acid; acetonitrile;

upstream raw materials:

(2,4,5-trifluorophenyl)acetic acid

4-(2,4,5-trifluoro-phenyl)-3-oxo-butyric acid methyl ester

(R)-methyl 3-hydroxy-4-(2,4,5-trifluorophenyl)butanoate

3(S)-4-(2,4,5-trifluorophenyl)-3-hydroxybutanoic acid

Downstream raw materials:

(R)-3-((benzyloxy)amino)-4-(2,4,5-trifluorophenyl)butanoic acid

sitagliptin phosphate

sitagliptin

sitagliptin phosphate monohydrate

Refernces

• 1、 -. "SITAGLIPTIN, SALTS AND POLYMORPHS THEREOF". . . Retrieved 2013/06/28.
• 2、 Hansen, Karl B.,Balsells, Jaume,Dreher, Spencer,Hsiao, Yi,Kubryk, Michele,Palucki, Michael,Rivera, Nelo,Steinhuebel, Dietrich,Armstrong III, Joseph D.,Askin, David,Grabowski, Edward J. J.. "First generation process for the preparation of the DPP-IV inhibitor sitagliptin". . p. 634 - 639. Retrieved 2012/12/25.