Ethyl isobutyrate → Ethyl 6-bromo-2,2-dimethylhexanoate

Temperature

-78 °C

In a 1-L 3-neck round-bottomed flask fitted with condenser, dropping funnel pressure equalizer and magnetic stirrer, purged with argon and maintained under argon, were added ethyl isobutyrate (84 ml, 0.63 mol) and THF (120 ml). The mixture was cooled to −78° C., when a solution of LDA (300 ml, 2.0 M in THF/heptane) was added dropwise with a syringe. After the addition was complete, the reaction mixture was stirred at −78° C. for 1 hr. To this mixture, 1,4-dibromobutane (105 ml, 0.84 mol) was added at −78° C., followed by HMPA (90 ml). The reaction mixture was stirred for 30 min at −78° C., then the cooling was stopped. The reaction was left to warm to room temperature, and was quenched with a saturated NH4Cl solution (1.8 L). The aqueous layer was extracted with ethyl acetate (3×100 ml), the organic extracts combined were washed with brine (100 ml), 5% HCl (100 ml) and saturated NaHCO3 (100 ml). The organic phase was dried (MgSO4) and the solvent was evaporated under vacuum. The residue was distilled under reduced pressure to provide the above-titled compound (105.2 g, 70%) (bp 65° C./0.15 mmHg). 1H NMR CDCl3, δ (ppm): 4.15 (q, J=4 Hz, 2H), 3.41 (t, J=5.3 Hz, 2H), 1.85 (qv, J=4 Hz, 2H), 1.60-1.45 (m, 2H), 1.40-1.30 (m, 2H), 1.28 (t, J=4 Hz, 3H), 1.20 (s, 6H); 13C NMR CDCl3, δ (ppm): 177.3, 60.0, 41.8; 39.4, 33.2, 32.9, 24.9, 23.34, 14.02.

1. customIn a 1-L 3-neck round-bottomed flask fitted with condenser
2. custompurged with argon
3. temperaturemaintained under argon
4. additionAfter the addition
5. stirringThe reaction mixture was stirred for 30 min at −78° C.
6. waitThe reaction was left
7. temperatureto warm to room temperature
8. customwas quenched with a saturated NH4Cl solution (1.8 L)
9. extractionThe aqueous layer was extracted with ethyl acetate (3×100 ml)
10. washthe organic extracts combined were washed with brine (100 ml), 5% HCl (100 ml) and saturated NaHCO3 (100 ml)
11. dry with materialThe organic phase was dried (MgSO4)
12. customthe solvent was evaporated under vacuum
13. distillationThe residue was distilled under reduced pressure

ORD record

ord-fc2720e192254dd8b1e27bf281d081e7

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06506799B1