ChemicalBook CAS DataBase List Oseltamivir phosphate

Oseltamivir phosphate synthesis

9synthesis methods

Product Name:Oseltamivir phosphate
CAS Number:204255-11-8
Molecular formula:C16H31N2O8P
Molecular Weight:410.4

Oseltamivir phosphate (Tamiflu) has been synthesized from cis-2,3-bis(hydroxymethyl)aziridine. After protection of the cis-2,3-bis(hydroxymethyl)aziridine with a Boc group, desymmetrization provided a chiral aziridine, which was a key intermediate to install the required stereogenic center containing a nitrogen atom. Allylation and ring closing metathesis are the key reactions to obtain the cyclic product that was successfully converted to the desired oseltamivir phosphate. DOI: 10.1021/jo3015853
synthesis of Oseltamivir phosphate

It can also be obtained by a novel 12-step synthesis from (-)-quinic acid.

196618-13-0 Synthesis

196618-13-0
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204255-11-8
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Yield:204255-11-8 98%

Reaction Conditions:

with phosphoric acid in ethanol at 50; for 0.0166667 h;Sonication;

Steps:

8 Reaction 8: Continuous flow synthesis of Oseltamivir Phosphate 3

Oseltamivir 33 was treated with FI2PO4 to afford Oseltamivir phosphate 3 (Scheme 18) in a continuous flow system. Scheme 19 (0204) A 0.8 ml PTFE coil reactor (0.8 mm ID, 1 .6 m tube length) under sonication was used to optimise the treatment of Oseltamivir 33 with H2PO4 affording Oseltamivir phosphate 3 in a continuous flow system. Oseltamivir 33 (0.1 M) in ethanol and H2PO4 (0.12 M, 1 .2 equiv.) in ethanol were pumped through a thermally controlled continuous flow system to afford oseltamivir phosphate. Samples were collected and analysed using HPLC method A. (0205) Oseltamivir 33 (0.1 M) in ethanol was treated with H2PO4 (0.12 M, 1 .2 equiv.) in ethanol at 50 °C in a 0.8 ml PTFE coil reactor (0.8 mm ID, 1 .6 m tube length) under sonication at various residence times for optimisation. The results of these experiments are shown in Figure 20. (0206) Conversion to Oseltamivir phosphate 3 increased with increase in residence time. A conversion plateau of 98 % (FIPLC) towards Oseltamivir phosphate 3 was reached at 60 s residence time. Based on these experiments, the preferred conditions were about 50 °C and 60 s residence time to give Oseltamivir phosphate 3 (98 %, FIPLC), which is a significant improvement an any previously reported reaction. (0207) This above description of some of the illustrative embodiments of the invention is to indicate how the invention can be made and carried out. Those of ordinary skill in the art will know that various details may be modified thereby arriving at further embodiments, but that many of these embodiments will remain within the scope of the invention.

References:

WO2020/183281,2020,A1 Location in patent:Page/Page column 7; 33; 34