D-Arabinonic acid, 2-C-methyl-4,5-O-(1-methylethylidene)-,ethyl ester Chemical Properties

Melting point:

75.0-75.5℃

Boiling point:

361.5±37.0 °C(Predicted)

Density 

1.185±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

12.29±0.29(Predicted)

Appearance

Off-white to light yellow Solid

D-Arabinonic acid, 2-C-methyl-4,5-O-(1-methylethylidene)-,ethyl ester Usage And Synthesis

Uses

2-C-Methyl-4,5-O-(1-methylethylidene)-D-arabinonic Acid Ethyl Ester can be?utilized for the synthesis of2''-deoxy-2''-fluoro-2''-C-methylcytidine (I) (PSI-6130), which is a potent and selective inhibitor of HCV NS5B polymerase. This product also has potential applications for the synthesis of related antiviral agents.

Synthesis

Compound 1t (54.0 g, 0.25 mol) and acetone (500 mL) were added to a 1000 mL three-neck flask. QAS-2 (11.4 g, 25.0 mmol) was then added. The reaction mixture was cooled to 0-5 °C. Solid KMnO4 (47.5 g, 0.3 mol) was added in batches over 10 minutes. The reaction mixture was stirred at this temperature for 2 h. The reaction was monitored by TLC until the feedstock 1t was completely consumed. Upon completion of the reaction, a one-time addition of aqueous (50 mL) solution of NaHSO3 (25.0 g) was added to quench the reaction. Stirring was continued for 15 min, then the filtrate was filtered through diatomaceous earth and the cake was washed thoroughly with acetone (3 x 100 mL). The filtrates were combined and concentrated under reduced pressure to remove the acetone. The residue was extracted with EtOAc (3 x 150 mL). The organic phases were combined, washed sequentially with saturated NaHCO3 solution and brine (3 x 50 mL), dried over anhydrous Na2SO4, filtered and concentrated to dryness under reduced pressure to give a colorless oil (57.5 g, 93% yield). The oily material was recrystallized by petroleum ether (200 mL) to give a white solid product in a yield of 51.3 g (83% yield) with a melting point of 75-76 °C. 1H NMR (400 MHz, CDCl3) data were as follows: δ= 4.20-4.31 (m, 3H), 4.09 (m, 2H), 3.93 (d, J = 8.0 Hz, 1H), 2.52 ( br, 2H), 1.31-1.49 (m, 12H).

References

[1] Synthesis (Germany), 2018, vol. 50, # 9, p. 1815 - 1819
[2] Patent: US2015/366888, 2015, A1. Location in patent: Paragraph 1101; 1103
[3] Patent: WO2014/59901, 2014, A1. Location in patent: Page/Page column 57
[4] Patent: WO2014/59902, 2014, A1. Location in patent: Page/Page column 56; 57
[5] Patent: CN106146433, 2016, A. Location in patent: Paragraph 0009; 0028

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