Ethyl bromoacetate → Ethyl 4-oxo-3-propanoylhexanoate

Temperature

0 °C

Dissolve heptane-3,5-dione (2.5 g, 19.5 mmol) in dry tetrahydrofuran (10 mL) and add the resulting solution dropwise to a chilled (0° C.) suspension of sodium hydride (0.94 g, 23.4 mmol, 60% dispersion in oil) in tetrahydrofuran (20 mL). Stir at 0° C. for 1 hr., then add bromoacetic acid ethyl ester (2.6 mL, 23.4 mmol) dropwise. Stir for 16 hr. at 0° C. and warm to room temperature. Partition the reaction mixture between diethyl ether (100 mL) and saturated aqueous ammonium chloride solution (50 mL). Separate the organic layer and wash with saturated aqueous sodium chloride solution (50 mL), dry (sodium sulfate), filter and concentrate. Purify using silica gel chromatography, eluting with 10:1 hexanes:ethyl acetate, to give 4-oxo-3-propionyl-hexanoic acid ethyl ester as an oil (3.2 g, 77%). 1H-NMR (400 MHz, CDCl3) δ 4.08 (m, 3H), 2.83 (d, 2H), 2.55 (q, 2H), 1.21 (t, 3H), 1.02 (t, 6H).

1. additionadd the resulting solution dropwise to
2. temperaturea chilled
3. stirringStir for 16 hr
4. temperatureat 0° C. and warm to room temperature
5. customPartition the reaction mixture between diethyl ether (100 mL) and saturated aqueous ammonium chloride solution (50 mL)
6. customSeparate the organic layer
7. washwash with saturated aqueous sodium chloride solution (50 mL)
8. dry with materialdry (sodium sulfate)
9. filtrationfilter
10. concentrationconcentrate
11. customPurify
12. washeluting with 10:1 hexanes

ORD record

ord-e5cf9ef8eeba4791a5c43d82a63ad79c

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08202873B2