methyl 1,4-dioxaspiro[4.5]decane-8-carboxylate

Uses

methyl 1,4-dioxaspiro[4.5]decane-8-carboxylate is a reagnet used in the preparation of pharmaceutical compounds such as high affinity H3 receptor agonists and reverse hydroxamate-based selective TACE inhibitors.

Synthesis

Step 1: Synthesis of methyl 1,4-dioxaspiro[4.5]decane-8-carboxylate 1.3 g of methyl 4-oxocyclohexanecarboxylate, 0.64 g of ethylene glycol and 0.14 g of p-toluenesulfonic acid were added to 40 mL of toluene. The mixed solution was refluxed and stirred overnight in the presence of a Dean-Stark water separator to remove the water generated. Upon completion of the reaction, the toluene solvent was removed by distillation under reduced pressure. Subsequently, the reaction mixture was separated by extraction with 50 mL of diethyl ether and 50 mL of water. The organic phase was dried with anhydrous magnesium sulfate, filtered and purified by reduced pressure distillation (138~145 °C, 15 mmHg) to afford 0.42 g of the oily target product methyl 1,4-dioxaspiro[4.5]decane-8-carboxylate. The product was characterized by NMR (300 MHz, CDCl3): δ 3.95 (s, 4H), 3.67 (s, 3H), 2.36~2.32 (m, 1H), 1.94~1.91 (m, 2H), 1.83~1.75 (m, 4H), 1.61~1.55 (m, 2H).

References

[1] Journal of Organic Chemistry, 1997, vol. 62, # 16, p. 5284 - 5292
[2] Recueil: Journal of the Royal Netherlands Chemical Society, 1980, vol. 99, # 2, p. 53 - 57
[3] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 23, p. 6309 - 6323
[4] Patent: WO2007/6760, 2007, A1. Location in patent: Page/Page column 109-110; 130-131
[5] Patent: EP1860089, 2007, A1. Location in patent: Page/Page column 21-22