ChemicalBook CAS DataBase List Arteether

Arteether synthesis

11synthesis methods

Product Name:Arteether
CAS Number:75887-54-6
Molecular formula:C17H28O5
Molecular Weight:312.4

Naphtho[1,2-b]furan-2,8(3H,4H)-dione, 3a,5,5a,6,7,9b-hexahydro-4-hydroxy-3,5a,9-trimethyl-, (3S,3aR,4S,5aR,9bS)-

108739-44-2

75887-54-6

The general procedure for the synthesis of (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-ethoxy-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isobenzofuran from artemisinin (CAS: 108739-44-2) was as follows: Example 1: Artemisinin (1.0 g) was dissolved in ethanol (20 mL) with polyhydroxy catalyst dextrose (5.0 g) and stirred at room temperature for 5 minutes. Subsequently, sodium borohydride (600 mg) was slowly added over 10 min and the reaction mixture was stirred for about 1 h at room temperature (20-23°C). The progress of the reaction was monitored by thin layer chromatography (TLC) to confirm the completion of the reduction step. The acid catalyst chlorotrimethylsilane (3.5 mL) was slowly added at 10-23°C. The reaction mixture was continued to be stirred at room temperature for about 1 hour. Upon completion of the reaction, cooling water (about 150 mL) was added to the mixture and the aqueous phase was extracted with a hexane solution of 1% ethyl acetate (3 x 50 mL). The combined ethyl acetate-hexane extract was washed sequentially with 0.5% sodium bicarbonate solution (100 mL) and water (50 mL). The hexane extract was dried over anhydrous sodium sulfate and the solvent was evaporated to give 1.038 g of the crude product, which contained artemether and a few impurities. The crude product was purified by silica gel column chromatography (silica gel 10 g, eluent 0.5% to 8% ethyl acetate in hexane solution) to give a mixture of α and β arteether 0.86 g (yield 86% w/w). A small amount of arteether was taken to separate the α and β isomers by preparative thin layer chromatography (TLC) and characterized by co-thin layer chromatography (Co-TLC) and spectral analysis.

122-51-0 Synthesis

122-51-0
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81496-81-3 Synthesis

81496-81-3
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75887-54-6
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Yield: 71.38%

Reaction Conditions:

Stage #1:orthoformic acid triethyl ester;dihydroartesiminin in ethanol at 20; for 0.25 h;
Stage #2: with acetyl chloride in ethanol at 10 - 15;
Stage #3: with sodium hydrogencarbonate in ethanol;water at 0 - 5; for 2 h;

Steps:

2
Dihydroartemisinin (25 g, 0.088 mole), ethanol (75 ml) and triethyl ortho formate (50 ml / 44.55 g = 0.301 mole) were stirred at ambient temperature for 15 minutes. The reaction mixture was cooled to 10-15°C and acetyl chloride (0.24 ml / 0.265 g =0.0034 mole) was added. Stirring was continued at 10-15°C for another 3hs or till the end of the reaction (monitoring by TLC). The reaction mixture was diluted with sodium bicarbonate solution (0.25g in 150 ml water). The reaction mass was then cooled to 0°C-5°C and stirred for 2 hours. The precipitated product was filtered and washed with ethanol: water (1 :1, 2 X 25 ml). The product was suck-dried and then recrystallised from ethanol: water (1:1) to get the title product as white crystalline solid. Yield: 19.6g, (71.38%); m.p.: 81°C-84°C; [α]_D²⁰: +155° to +157° (2% solution in dehydrated ethanol). HPLC purity > 99%¹HNMR : δ 0.91 (doublet, 3H), δ 0.96 (doublet, 3H), δ 1.16-1.18 (triplet, 3H), δ 1.21-1.34 (multiplet, 3H), δ 1.44 (singlet, 3H), δ 1.47-1.62 (multiplet, 2H), δ 1.65-1.66 (multiplet, IH), δ 1.7-1.91 (multiplet, 3H), δ 2.01-2.06 (multiplet, IH), δ 2.32-2.38 (multiplet, IH), δ 2.62-2.64 (multiplet, IH), δ 3.43 & 3.86 (multiplet, 2H), δ 4.80 (doublet, IH), δ 5.41 (singlet, IH)

References:

CALYX CHEMICALS AND PHARMACEUTICALS LTD. WO2009/109989, 2009, A1 Location in patent:Page/Page column 10