trans-1-(4-Fluorophenyl)-3-(3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one

Base Information

• Chemical Name: trans-1-(4-Fluorophenyl)-3-(3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one
• CAS No.: 163222-33-1
• Molecular Formula: C24H21F2NO3
• Molecular Weight: 409.432
• Hs Code.: 29337900
• NSC Number: 758923
• Wikidata: Q27163509
• Mol file: 163222-33-1.mol

Synonyms:1228746-78-8;trans-1-(4-Fluorophenyl)-3-(3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one;Spectrum_001804;Spectrum2_000489;Spectrum3_001005;Spectrum4_001133;Spectrum5_001552;BSPBio_002729;KBioGR_001645;KBioSS_002297;SCHEMBL528037;SPECTRUM1505203;SPBio_000357;CHEBI:91688;KBio2_002295;KBio2_004863;KBio2_007431;KBio3_001949;HMS1922L11;HMS2093K14;Pharmakon1600-01505203;(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-2-azetidinone;CCG-39521;NSC758923;NCGC00178504-01;SBI-0206742.P001;AB01563046_01;SR-05000001984;SR-05000001984-1;BRD-A41519720-001-02-2;Q27163509

Chemical Property of trans-1-(4-Fluorophenyl)-3-(3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 4.83E-18mmHg at 25°C
• Melting Point: 164-166 °C
• Refractive Index: 1.623
• Boiling Point: 654.9 °C at 760 mmHg
• PKA: 9.72±0.30(Predicted)
• Flash Point: 349.9 °C
• PSA: 60.77000
• Density: 1.334 g/cm³
• LogP: 4.95330
• Storage Temp.: -20?C Freezer
• Solubility.: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 15 mg/ml)
• XLogP3: 4
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 409.14894986
• Heavy Atom Count: 30
• Complexity: 567

Purity/Quality:

99.0% MIN ^*data from raw suppliers

Ezetimibe ^*data from reagent suppliers

Safty Information:

• Pictogram(s): R36/37/38:
• Hazard Codes: R36/37/38:
• Statements: 36/37/38
• Safety Statements: 26-36-24/25

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CC(=CC=C1C2C(C(=O)N2C3=CC=C(C=C3)F)CCC(C4=CC=C(C=C4)F)O)O
• Isomeric SMILES: C1=CC(=CC=C1[C@@H]2[C@H](C(=O)N2C3=CC=C(C=C3)F)CCC(C4=CC=C(C=C4)F)O)O
• Mechanism of Action: Ezetimibe is a cholesterol absorption inhibitor that targets LDL-C uptake at the jejunal enterocyte brush border. It primarily acts on the cholesterol transport protein Nieman Pick C1-like 1 protein (NPC1L1P). By inhibiting cholesterol absorption, ezetimibe reduces LDL-C levels in the bloodstream.
• Safety and Tolerability: Ezetimibe is generally safe and well-tolerated. Studies comparing ezetimibe with placebo, usual care, or other lipid-lowering agents showed little to no difference in adverse events or undesirable effects.
• Combination Therapy: Ezetimibe is often used in combination with statins to achieve a cumulative reduction in LDL-C levels.; The combination of ezetimibe with rosuvastatin has been found to be safe and effective in patients with hypercholesterolemia or dyslipidemia, with or without diabetes or cardiovascular disease.; The combination therapy has shown to enable higher proportions of patients to achieve recommended LDL-C goals compared to monotherapy with rosuvastatin or simvastatin/ezetimibe.
• Clinical Efficacy: Clinical trials have demonstrated that the rosuvastatin/ezetimibe combination is significantly more effective than rosuvastatin monotherapy or simvastatin/ezetimibe in reducing LDL-C and total cholesterol levels in patients with hypercholesterolemia. The combination therapy has also been associated with improved hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD), particularly in individuals with higher BMI, type 2 diabetes mellitus, insulin resistance, and severe liver fibrosis.
• Approval and Evaluation: The 40 mg rosuvastatin/10 mg ezetimibe fixed combination has been approved and evaluated for its efficacy and safety in managing hypercholesterolemia and dyslipidemia in adults.

Technology Process of trans-1-(4-Fluorophenyl)-3-(3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one

There total 140 articles about trans-1-(4-Fluorophenyl)-3-(3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one 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: 99.0%

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone (163222-32-0) → ezetemibe (163222-33-1,1478664-18-4,1593543-00-0,1593543-07-7,1478664-02-6)

Guidance literature:

With 10 wt% Pd(OH)2 on carbon; hydrogen; In methanol; cyclohexane; at 70 ℃; for 3h; under 760.051 Torr;

Reference yield: 92.0%

4-((2S,3R)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-oxoazetidin-2-yl)phenyl pivalate (1232148-26-3) → ezetemibe (163222-33-1,1478664-18-4,1593543-00-0,1593543-07-7,1478664-02-6)

Guidance literature:

4-((2S,3R)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-oxoazetidin-2-yl)phenyl pivalate; With sodium hydroxide; In tetrahydrofuran; methanol; at -15 ℃;

With hydrogenchloride; water; In ethyl acetate;

Reference yield: 91.0%

C39H45ClF2N2O5Si2 → ezetemibe (163222-33-1,1478664-18-4,1593543-00-0,1593543-07-7,1478664-02-6)

Guidance literature:

With N,O-bis-(trimethylsilyl)-acetamide; tetrabutyl ammonium fluoride; In tert-butyl methyl ether; at 20 ℃; for 0.25h;

upstream raw materials:

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

[14C]-Sch 57871

(3R,4S)-4-(4-(trimethylsilyloxy)phenyl)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one

Downstream raw materials:

4(S)-(4-acetyloxyphenyl)-3(R)-(3(S)-acetyloxy-3-(4-fluorophenyl)propyl)-1-(4-fluorophenyl)-2-azetidinone

1-(4-fluorophenyl)-(3R)-[(4-fluorophenyl)-(2E)-propenyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone

(3R,4S)-4-[4-(4-bromomethylbenzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one

1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone hydrate

Refernces

• 1、 -. "METHOD OF PREPARING EZETIMIBE AND INTERMEDIATE THEREOF". Paragraph 0080-0082. . Retrieved 2019/08/30.
• 2、 -. "Preparation method of ezetimibe for treating hyperlipidemia". Paragraph 0021; 0027; 0028; 0034; 0035; 0041; 0042. . Retrieved 2018/03/25.