Hexanoyl chloride → 3-Ketooctanoic acid

A stirred solution of bis-trimethylsilyl malonate (21.6 g, 71.5 mmol) in 100 mL of anhydrous diethyl ether was cooled to −78° C. To this solution, n-butyl lithium (1.6 M in ether, 44.7 mL, 71.5 mmol) was added slowly, keeping the temperature below −60° C. Upon completion of addition, the reaction was allowed to warm to −10° C., at which time hexanoyl chloride (5 mL, 35.75 mmol) was added quickly and allowed to stir for 30 minutes. Next, 150 mL of a cold, aq. 5% sodium bicarbonate solution was added, and the resulting solution was stirred vigorously for 30 minutes. The aq. layer was separated out and acidified with cold 4N sulfuric acid until pH=2. The aq. layer was then extracted 2×50 mL with diethyl ether, dried over MgSO4, and concentrated down in vacuo to afford a white solid. This solid could be further purified by recrystallization from hexane, if necessary. 4.9 g, 87% yield. 1H NMR (300 MHz, CDCl3) δ=3.49 (s, 2H, CH2), 2.59 (t, 2H, J=7.3 Hz, CH2), 1.64 (p, 2H, J=7.4 Hz, CH2), 1.34 (m, 4H, CH2CH2), 0.92 (t, 3H, J=6.9 Hz, CH3); 13C NMR (75 MHz, CDCl3) δ=204.4, 182.8, 87.9, 48.1, 43.4, 31.3, 23.5, 14.1 ppm.

1. customthe temperature below −60° C
2. additionUpon completion of addition
3. additionwas added quickly
4. stirringthe resulting solution was stirred vigorously for 30 minutes
5. customThe aq. layer was separated out
6. extractionThe aq. layer was then extracted 2×50 mL with diethyl ether
7. dry with materialdried over MgSO4
8. concentrationconcentrated down in vacuo
9. customto afford a white solid
10. customThis solid could be further purified by recrystallization from hexane

ORD record

ord-5b25d22c94364953849269e7446030b1

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08269024B2