((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate Chemical Properties

Melting point:

133℃

Boiling point:

458.6±34.0 °C(Predicted)

Density 

1.33

storage temp. 

2-8°C

Appearance

White to yellow Solid

InChI

InChI=1/C20H17FO6/c1-20(21)16(27-18(23)14-10-6-3-7-11-14)15(26-19(20)24)12-25-17(22)13-8-4-2-5-9-13/h2-11,15-16H,12H2,1H3/t15-,16-,20-/s3

InChIKey

OUKYMZJNLWKCSO-ZFVYKOPKNA-N

SMILES

C([C@H]1OC(=O)[C@@](F)(C)[C@@H]1OC(C1C=CC=CC=1)=O)OC(C1C=CC=CC=1)=O |&1:1,5,8,r|

((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate Usage And Synthesis

Uses

neuromuscular blocking agent

Uses

(2R)-2-Deoxy-2-fluoro-2-methyl-D-erythropentonic Acid γ-Lactone 3,5-Dibenzoate is a reactant used in the synthesis of 1''-C-cyano-2''-fluoro-2''-C-methyl pyrimidine nucleosides as HCV polymerase inhibitors.

Application

((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate is an impurity of Sofosbuvir. Sofosbuvir is a NS5B inhibtor used for the treatment of hepatitis C. It is only recommended with some combination of ribavirin, peginterferon-alfa, simeprevir, ledipasvir or daclatasvir.

Synthesis

(3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyldihydrofuran-2(3H)-one (60 mg, 0.16 mmol) was dissolved in anhydrous pyridine (1 mL) and benzoyl chloride (0.3 mL) was added slowly. The reaction mixture was stirred at room temperature for 20 min, then water (1 mL) was added and stirring was continued for 20 min. The reaction solution was diluted with ethyl acetate (5 mL) and washed sequentially with water (2 mL) and 1M HCl (2 mL x 3). The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=10:1) to afford ((2R,3R,4R)-3-(benzyloxy)-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate (118 mg, 87% yield) as a white solid.1H NMR (CDCl3) δ (ppm): 8.08 (m, 2H. Ar-H), 7.99 (m, 2H, Ar-H), 7.63 (m, 1H, Ar-H), 7.58 (m, 1H, Ar-H), 7.49 (m, 2H, Ar-H), 7.43 (m, 2H, Ar-H), 5.51 (dd, 1H, J=7.2,17.6Hz, H-3), 5.00 (m, 1H, H-4). 4.78 (dd, 1H, J=3.6,12.8Hz, H-5), 4.59 (dd, 1H, J=5.2,12.8Hz, H-5'), 1.75 (d, 3H, J=23.6Hz, CH3-2).

References

[1] Patent: WO2006/31725, 2006, A2. Location in patent: Page/Page column 13; 30-31
[2] Patent: CN105418547, 2016, A. Location in patent: Paragraph 0019; 0020
[3] Patent: CN106146433, 2016, A. Location in patent: Paragraph 0009; 0025
[4] Patent: CN107573304, 2018, A. Location in patent: Paragraph 0120-0124
[5] Patent: WO2014/108525, 2014, A1. Location in patent: Page/Page column 18

((2R,3R,4R)-3-(benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate(874638-80-9)Related Product Information

• D-Alanine, N-[[P(S),2'R]-2'-cyano-2'-deoxy-2'-Methyl-P-phenyl-5'-cytidylyl]-, 1-Methylethyl ester
• Cytidine,N-benzoyl-2^-C-Methyl-,3^,5^-dibenzoate(9CI)
• Sofosbuvir Impurity 17
• L-Alanine, N-[(R)-(2,3,4,5,6-pentafluorophenoxy)phenoxyphosphinyl]-, 1-Methylethyl ester
• (3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxyMethyl)-3-Methyl-dihydrofuran-2(3H)-one
• N-[(S)-(2,3,4,5,6-pentafluorophenoxy)phenoxyphosphinyl]-L-alanine 1-Methylethyl ester
• L-Alanine isopropyl ester hydrochloride
• (2'R)-2'-Deoxy-2'-fluoro-2'-Methyl-uridine 3',5'-dibenzoate
• PSI-6130 derivative
• D-Arabinonic acid, 2-C-methyl-4,5-O-(1-methylethylidene)-,ethyl ester
• 2'-deoxy-2'-fluoro-2'-C-methyluridine
• Sofosbuvir
• alpha-D-erythro-Pentofuranous-2-ulose 1,3,5-tribenzoate
• sofosBuvir impurity 36
• SofosBuvir Impurity 55
• Sofosbuvir impurity E
• SofosBuvir Impurity 40
• SofosBuvir Impurity 54