40052-13-9

Clear light yellow liquid

tert-Butyl hydrogen malonate may be used in the preparation of dendritic precursor to asymmetric methanofullerenes, hapten-3,6-(O,S-dimethylthiophosphoramido)-6-oxohexanoic acid, hapten-4,3-(O,S-dimethylthiophosphoramido)-3-oxopropanoic acid.

1. Malonic acid (5.0 g, 48 mmol) and tert-butanol (1.8 mL, 19 mmol) were dissolved in 150 mL of acetonitrile (ACN) under nitrogen protection and stirred at room temperature. 2. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC, 9.2 g, 48 mmol) was added and the reaction was continued for 30 minutes at room temperature under nitrogen atmosphere. 3. After completion of the reaction, acetonitrile was removed by distillation under reduced pressure. 4. The residue was dissolved in 200 mL of ether and back-extracted with two 50 mL portions of saturated sodium bicarbonate (NaHCO3) solution. 5. The aqueous phases were combined and acidified to pH 2 with 1N sodium bisulfate solution. 6. Extract the acidified aqueous phase with three 200 mL portions of dichloromethane (DCM) and combine the organic phases. 7. Wash the combined organic phases with water and saturated saline in turn, and then dry with anhydrous sodium sulfate. 8. Dichloromethane was removed by pressure-reduced distillation to give monotert-butyl malonate as a white solid product in 76% (2.3 g) yield. 9. 9. The product was characterized by 1H NMR (CDCl3, 400 MHz): δ 3.28 (s, 2H), 1.42 (s, 9H); 13C NMR (CDCl3, 100 MHz): δ 168.5, 162.1, 83.5, 39.7, 27.9, 27.8, 25.6.

[1] Journal of Organic Chemistry, 2018, vol. 83, # 3, p. 1116 - 1133
[2] Patent: WO2018/144880, 2018, A1. Location in patent: Paragraph 72-73
[3] Journal of Medicinal Chemistry, 2006, vol. 49, # 17, p. 5273 - 5281
[4] Patent: US2006/211634, 2006, A1. Location in patent: Page/Page column 15
[5] Organic and Biomolecular Chemistry, 2008, vol. 6, # 19, p. 3561 - 3572