Reaction #76264

Reaction equation

Ethyl (4-isobutyl-phenyl)-acetate

Lithium diisopropylamide

1,4-Dibromobutane

→

6-bromo-2-(4-isobutyl-phenyl)-2-methyl-hexanoic acid ethyl ester

Yield 87.6%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   Temperatureto warm to room temperature over five hours
2. 2
   workup.STIRRINGAfter stirring at room temperature for an additional 16 hours
3. 3
   Otherthe reaction was quenched with water (100 mL)
4. 4
   Extractionextracted with diethyl ether (2×100 mL)
5. 5
   WashThe ether was washed with 10% hydrochloric acid (2×100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL)
6. 6
   DryingAfter drying with sodium sulfate (5 g), filtration and concentration
7. 7
   Otherthe product was purified by flash chromatography on silica gel (200 g)
8. 8
   Washeluting with 5% ethyl acetate/hexanes
9. 9
   TemperatureThe product was then heated to 150° C. under vacuum (0.5 mm Hg) for 30 minutes
10. 10
    Otherto remove excess 1,4-dibromobutane

Procedure

Ethyl (4-isobutyl-phenyl)-acetate (10.5 g, 44.8 mmol) was dissolved in freshly distilled tetrahydrofuran (150 mL) and cooled to −78° C. Lithium diisopropylamide (2 N, 28 mL, 56 mmol) was added and the solution stirred for 1 hour at −78° C. under a nitrogen atmosphere. 1,4-Dibromobutane (25 mL, 37.5 g, 175 mmol) was then added drop-wise over 30 minutes. The solution was allowed to warm to room temperature over five hours. After stirring at room temperature for an additional 16 hours, the reaction was quenched with water (100 mL) and extracted with diethyl ether (2×100 mL). The ether was washed with 10% hydrochloric acid (2×100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL). After drying with sodium sulfate (5 g), filtration and concentration, the product was purified by flash chromatography on silica gel (200 g), eluting with 5% ethyl acetate/hexanes. The product was then heated to 150° C. under vacuum (0.5 mm Hg) for 30 minutes to remove excess 1,4-dibromobutane. The reaction yielded 6-bromo-2-(4-isobutyl-phenyl)-2-methyl-hexanoic acid ethyl ester (14.49 g, 87.5% yield) as a clear, viscous oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 7.19 (d, 2H, J=8.0 Hz), 7.08 (d, 2H, J=8.0 Hz), 4.11 (q, 2H, J=7.0 Hz), 3.35 (t, 2H, J=6.8 Hz), 2.43 (d, 2H, J=7.3 Hz), 2.10-1.92 (m, 1H), 1.92-1.78 (m, 4H), 1.53 (s, 3H), 1.40-1.28 (m, 2H), 1.17 (t, 3H, J=7.0 Hz), 0.88 (6H, J=6.8). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm) 176.17, 141.12, 140.04, 129.14, 125.64, 60.77, 49.80, 44.99, 38.52, 33.51, 33.26, 30.22, 23.55, 22.69, 22.50, 14.19. HRMS (LSIMS, nba): Calcd. for C19H30O2Br (MH+): 369.1429, found: 369.1445.

Source