Chloroacetyl chloride → HCID 23500892, compound

Temperature

0 °C

Anhydrous ZnCl2 (5.0 g, 37 mmol) was dissolved in TBF (25 mL) and the solution cooled to 0° C. in an ice bath. In another flask 1-ethynylcyclohexene (4.3 mL, 36.3 mmol) was dissolved in THF (25 mL), cooled to 0° C. in an ice bath, and treated with n-butyllithium (15.7 mL of a 2.2M solution in hexane, 34.5 mmol). After 20 minutes the cyclohexenylethynyllithium solution was added via cannula to the ZnCl2 solution. After an additional 20 minutes Pd(PPh3)4 (620 mg, 0.54 mmol) was added to the alkynylzinc solution. The resulting yellow solution was treated with chloroacetyl chloride (4.2 mL, 55 mmol) dropwise over 10 minutes. After 2 h at 0° C. the reaction mixture was quenched by the addition of saturated aqueous NH4Cl (500 mL), and diluted with ethyl acetate. The aqueous phase was extracted with ethyl acetate (3.times.200 ml) and the combined organic layers were washed with water (200 ml), brine (200 ml), dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to afford a dark brown oil that was purified by column chromatography eluting with hexane, then 99:1 hexane:ethyl acetate to afford 1-chloro-4-(1-cyclohexen-1-yl)-3-buty-n-2-one (4.4 g, 67% yield) as an orange oil. 1H NMR (CDCl3, 300 MHz) Δ6.56 (m, 1H), 4.23 (s, 2H), 2.19 (m, 4H), 1.68-1.62 (m, 4H). MS (EI ionization) 182 (35Cl M+), 184 (37Cl M+). The material was carried on to the next step without further purification.

1. temperaturecooled to 0° C. in an ice bath
2. customAfter 2 h at 0° C. the reaction mixture was quenched by the addition of saturated aqueous NH4Cl (500 mL)
3. additiondiluted with ethyl acetate
4. extractionThe aqueous phase was extracted with ethyl acetate (3.times.200 ml)
5. washthe combined organic layers were washed with water (200 ml), brine (200 ml)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationThe filtrate was concentrated in vacuo
9. customto afford a dark brown oil that
10. customwas purified by column chromatography
11. washeluting with hexane

ORD record

ord-989d9eeb4a364fc7b50345e444461bb5

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07365074B2