Formaldehyde → 4-Methyl-2-methylene valeric acid

To neat ethyl isobutylmalonate (25 g, 0,13 mol) at 0° was slowly added ice cold diethylamine (15.1 mL, 0.15 mol). After stirring for 15 min, formalin (11,1 mL 37% aqueous formaldehyde) was added dropwise. The mixture was allowed to stir at 25° for 3 days. The reaction mixture was then treated with a solution of 20 g of K2CO3 in 40 mL of water and extracted with ether (2×100 mL). The ether extracts were combined, washed with brine, dried over MgSO4 and concentrated under reduced pressure at 20°. The crude product, ethyl 4-methyl-2-methylenepentanoate containing some ether, was dissolved in absolute ethanol (250 mL) and treated with acetonitrile (250 mL), 1M LiOH (9.7 g in 250 mL of water, 0.23 mol). After stirring overnight, the organic solvents were evaporated under reduced pressure and the aqueous residue was extracted with ethyl acetate (2×150 mL). The combined extracts were washed with brine, dried over MgSO4 and concentrated under reduced pressure to afford 10.5 g of 4-methyl-2-methylenepentanoic acid as a colorless oil.

1. customat 0°
2. stirringto stir at 25° for 3 days
3. extractionextracted with ether (2×100 mL)
4. washwashed with brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure at 20°
7. dissolutionThe crude product, ethyl 4-methyl-2-methylenepentanoate containing some ether, was dissolved in absolute ethanol (250 mL)
8. stirringAfter stirring overnight
9. customthe organic solvents were evaporated under reduced pressure
10. extractionthe aqueous residue was extracted with ethyl acetate (2×150 mL)
11. washThe combined extracts were washed with brine
12. dry with materialdried over MgSO4
13. concentrationconcentrated under reduced pressure

ORD record

ord-a1de888823cf45f89f1ea605abbc95a4

Source dataset

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05773428