Formaldehyde → 4-Methyl-2-methylene valeric acid

To neat ethyl isobutylmalonate (25 g, 0.13 mol) at 0 C. was slowly added ice cold diethylamine (15.1 mL, 0.15 mol). After stirring for 15 minutes, formalin (11.1 mL of 37% aqueous formaldehyde) was added dropwise and the mixture was allowed to stir at 25° C. for 3 days. The reaction was treated with a solution of 20 g of K2CO3 in 40 mL of H2O and extracted with ether (2×100 mL). The combined ether layers were washed with brine, dried over MgSO4, and evaporated at 20° C. on a rotary evaporator. The crude product ethyl 4-methyl-2-methylenepentanoate (containing some ether) was dissolved in 250 mL of absolute ethanol and treated with acetonitrile (250 mL), 1M LiOH (9.7 g in 250 mL of H2O, 0.23 mol). After stirring overnight, the organic solvents were evaporated and the aqueous residue was extracted with ethyl acetate (2×150 mL). The combined extracts were washed with brine, dried (MgSO4), and evaporated to afford 10.5 g of 4-methyl-2-methylenepentanoic acid as a colorless oil.

1. stirringto stir at 25° C. for 3 days
2. extractionextracted with ether (2×100 mL)
3. washThe combined ether layers were washed with brine
4. dry with materialdried over MgSO4
5. customevaporated at 20° C. on a rotary evaporator
6. additionThe crude product ethyl 4-methyl-2-methylenepentanoate (containing some ether)
7. dissolutionwas dissolved in 250 mL of absolute ethanol
8. stirringAfter stirring overnight
9. customthe organic solvents were evaporated
10. extractionthe aqueous residue was extracted with ethyl acetate (2×150 mL)
11. washThe combined extracts were washed with brine
12. dry with materialdried (MgSO4)
13. customevaporated

ORD record

ord-086a8f011f534ae6a72b4d3893a69131

Source dataset

uspto-grants-2000_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06037472