(4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone Chemical Properties

Melting point:

90.0 to 94.0 °C

Boiling point:

568.4±50.0 °C(Predicted)

Density 

1.288±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

solubility 

soluble in Acetone

form 

powder to crystal

pka

-3.11±0.40(Predicted)

color 

White to Light yellow

optical activity

Consistent with structure

InChI

InChI=1S/C20H18FNO4/c21-16-11-9-15(10-12-16)18(23)7-4-8-19(24)22-17(13-26-20(22)25)14-5-2-1-3-6-14/h1-3,5-6,9-12,17H,4,7-8,13H2/t17-/m1/s1

InChIKey

XXSSRSVXDNUAQX-QGZVFWFLSA-N

SMILES

C(C1=CC=C(F)C=C1)(=O)CCCC(N1[C@@H](C2=CC=CC=C2)COC1=O)=O

CAS DataBase Reference

189028-93-1(CAS DataBase Reference)

Safety Information

HS Code 

2934.99.4400

(4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone Usage And Synthesis

Chemical Properties

Off-White Solid

Uses

3-[5-(1,5-Dioxo-5-(p-fluophenylpentyl]-4(S)-phenyl-2-oxazolidinone (cas# 189028-93-1) is a compound useful in organic synthesis.

Application

(4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone is a core chiral building block in the synthetic route of ezetimibe. Ezetimibe reduces blood cholesterol by inhibiting intestinal cholesterol absorption and is commonly used for the treatment of primary hypercholesterolemia and other related conditions. This intermediate is used to construct the key carbon chain and chiral center of the drug molecule. Through subsequent reactions such as condensation, reduction and cyclization, key groups including fluorophenyl and oxazolidinone are introduced, and finally the core structure of ezetimibe is formed via ring closure.

Synthesis

Example 1: Preparation of ezetimibe; (1-1) Preparation of (4S)-3-[5-(4-fluorophenyl)-1,5-dioxopentyl]-4-phenyl-2-oxazolidinone (Eq. 7); A reaction mixture was prepared by dissolving 200 g of 5-(4-fluorophenyl)-5-oxopentanoic acid (Eq. 8), 160 g of (S)-4-phenyl-oxazolidin-2-one (Eq. 9), and 11.6 g of 4- dimethylamino pyridine were dissolved in 600 mL of dichloromethane to prepare the reaction mixture. A solution prepared by dissolving 157 g of N,N'-dicyclohexylcarbimide in 200 mL of dichloromethane was added to the reaction mixture and stirred for 2 hours. Upon completion of the reaction, the resulting reaction mixture was filtered to remove the by-products. The filtrate was washed sequentially with 1 L of 6N HCl, 1 L of water and 1 L of saturated sodium chloride solution, dried with anhydrous magnesium sulfate, filtered and the solvent was removed by distillation under reduced pressure. The residue was dissolved in 2 L of methanol by heating and cooled to induce crystallization. 2L of water was added and stirred for 30 minutes. The solid was separated by filtration to give 289 g of (4S)-3-[5-(4-fluorophenyl)-1,5-dioxopentyl]-4-phenyl-2-oxazolidinone as a white solid (yield: 86%).1H NMR (300 MHz, CDCl3): δ 7.92 (2H, m), 7.35-7.13 (5H, m), 7.04 (2H, m). 5.43 (1H, q), 4.75 (1H, t), 4.22 (1H, q), 3.05-2.93 (4H, m), 2.03 (2H, m).

References

[1] Patent: WO2010/71358, 2010, A2. Location in patent: Page/Page column 14-15
[2] Patent: WO2006/122216, 2006, A2. Location in patent: Page/Page column 41-42
[3] Synthetic Communications, 2016, vol. 46, # 20, p. 1687 - 1693
[4] Patent: CN106397292, 2017, A. Location in patent: Paragraph 0053; 0086; 0087
[5] Patent: CN104513187, 2017, B. Location in patent: Paragraph 0063; 0064; 0065; 0066

(4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone(189028-93-1)Related Product Information

• Ezetimibe
• Methyl (3R,4S)-1-(4-fluorophenyl)-2-oxo-4-[4-(phenylmethoxy)phenyl]-3-azetidinepropanoate
• (3R,4S)-1-(4-Fluorophenyl)-2-oxo-4-[4-(benzyloxy)phenyl]-3-azetidinepropanoic acid
• PHENYL VALERATE
• TERT-AMYL METHYL ETHER
• Cyclopentanecarbaldehyde
• TETRAPENTYLAMMONIUM BROMIDE
• Oxadixyl
• EZETIMIBE-D4
• 1,5-Pentanedione, 1-(3-fluorophenyl)-5-[(4S)-2-oxo-4-phenyl-3-oxazolidinyl]-
• PHENYL RESIN
• 4-(4-Fluorobenzoyl)butyric acid
• (4S)-3-[(5R)-5-(4-FLUOROPHENYL)-5-HYDROXYPENTANOYL]-4-PHENYL-1,3-OXAZOLIDIN-2-ONE
• 4-[[(4-Fluorophenyl)imino]methyl]-phenol
• 5-(4-FLUOROPHENYL)VALERIC ACID
• ent-EzetiMibe
• EzetiMibe (3R,4R,3'S)-IsoMer
• (R)-3-((S)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one