Ammonium Chloride → 2-(1-Ethyl-1-methyl-propyl)-malonic acid dimethyl ester

Step A To a suspension of CuI (5.7 g, 30 mmol) in anhydrous tetrahydrofuran (100 mL) at −50° C. was added methylmagnesium chloride (3 M, 20 mL, 60 mmol) during a period of 15 min. After the addition was finished, the reaction mixture was gradually warmed room temperature and stirred for 20 min. Then the temperature of the mixture was lowered to −50° C., a tetrahydrofuran solution (20 mL) of 2-(1-ethyl-propylidene)-malonic acid dimethyl ester (3 g, 15 mmol) prepared in Example 106a Step A was added. The reaction mixture was allowed to slowly warmed to room temperature and stirred for 1 h. Aqueous saturated NH4Cl solution was added to quench the reaction. The mixture was filtered, and the filtrate was concentrated to remove most of tetrahydrofuran. The residue was extracted with ethyl acetate twice. The organic layers were combined, concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:30) to give 2-(1-ethyl-1-methyl-propyl)-malonic acid dimethyl ester as a colorless oil (3 g, 93%).

1. additionAfter the addition
2. customwas gradually warmed room temperature
3. customwas lowered to −50° C.
4. stirringstirred for 1 h
5. customto quench
6. customthe reaction
7. filtrationThe mixture was filtered
8. concentrationthe filtrate was concentrated
9. customto remove most of tetrahydrofuran
10. extractionThe residue was extracted with ethyl acetate twice
11. concentrationconcentrated
12. customThe residue was purified by chromatography (EtOAc:hexanes=1:30)

ORD-Eintrag

ord-58e0cf66a6d541118ed7f02157f455b1

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08354444B2