C-Alkylation
A 1.6 M solution of n-butyllithium in hexane (9.36 mL) was added to a stirred solution of diisopropylamine (2.22 mL) in THF (15 mL) at -5 to 0 oC. After being stirred at -5 to 0 oC for 30 min, the reaction mixture was cooled to -78 oC and ethyl isobutyrate (1.9 mL) was added. Stirring was continued at -78 oC for 45 min. A solution of 1-bromo-2-chloroethane (1.19 mL) in THF (1 mL) was then added dropwise to the mixture. The whole was further stirred at -78 oC for 1 h and at room temperature for 2 h, then poured into an excess of aqueous NH4Cl solution and extracted with ethyl acetate, the extract was washed with brine, dried over MgSO4, and evaporated in vacuum to give a residue, which was distilled to give ethyl 4-chloro-2,2-dimethylbutanoate isolated as a colorless oil, 2.1 g. NMR complies.
Ref: Chem. Pharm. Bull. 1997, 45, 1447-1457.
very nice. The only comment I have is that LDA formation is instantenious at 0C – no need to stirr it for extra 30 min on ice. You can also make LDA at -78C (in which case you need to give it about 30 min time).
milkshake
July 14, 2008 at 7:15 pm
Thank you. I also carried out this reaction with 1,2-dibromoethane (in place of 1-bromo-2-chloroethane) and isolated ethyl 4-bromo-2,2-dimethylbutanoate in excellent yield.
pmgb
July 14, 2008 at 8:08 pm
i would be grateful for yield in % of theor. because i am lazy to calculate it myself
petr
July 17, 2008 at 3:14 pm
on the other hand i must admit that writing of the post took me more time than the calculation
petr
July 17, 2008 at 3:14 pm
84.3%
pmgb
July 17, 2008 at 4:04 pm
Excellent. I mean, this whole blog. Keep it up.
Frank
August 15, 2008 at 8:21 pm
Thanks.
pmgb
August 15, 2008 at 9:40 pm