Sulfuric Acid → HCID 56952340, compound

Temperature

-50 °C

A mixture of 4-chlorophenyacetonitrile (1 gr. 5.37 mmol), DBU (14 mg) and acetone (2 mL) was warmed to reflux for ˜6-7 minutes, cooled, and diluted with 3 mL of butyl chloride. The solution was treated with 3 drops of 3N HCl, washed with water and saturated NaCl solution and the organic layer was filtered through a small pad of anhydrous magnesium sulfate. The resulting solution was chilled to −50° C. and seeded with the starting nitrile. After crystallization was complete, the supernatant liquid was withdrawn. The resulting wet solid was allowed to partially melt, then re cooled and again the supernatant liquid was withdrawn The solid was allowed to melt and stripped of solvent to return 0.75 g starting nitrile which was retreated with acetone and DBU, reacted and worked up as above. The combined supernatant was stripped to an oil. This was dissolved in one mL of acetonitrile, treated with 0.3 mL of acetic anhydride, then stirred with a m.p. tube with tip wetted with conc. H2SO4 to give a slow exotherm to ˜35° C. This was heated briefly to ˜80° C., cooled, and 0.5 mL of ethanol added to remove excess acetic anhydride. The mixture was diluted with 3 mL of ethyl acetate, washed with water, dried (MgSO4) and stripped to an oil. The oil was purified by radial chromatography using butyl chloride followed by a hexane-ethyl acetate gradient. Stripping pure fractions returned 110 mg. Rf 0.4 (silica gel, EtOAc/hexane=¼) of the desired ester.

1. temperaturewas warmed
2. temperatureto reflux for ˜6-7 minutes
3. temperaturecooled
4. washwashed with water and saturated NaCl solution
5. filtrationthe organic layer was filtered through a small pad of anhydrous magnesium sulfate
6. customAfter crystallization
7. customthe supernatant liquid was withdrawn
8. temperaturere cooled
9. customagain the supernatant liquid was withdrawn The solid
10. customreacted
11. customto give a slow exotherm to ˜35° C
12. temperatureThis was heated briefly to ˜80° C.
13. temperaturecooled
14. customto remove excess acetic anhydride
15. additionThe mixture was diluted with 3 mL of ethyl acetate
16. washwashed with water
17. dry with materialdried (MgSO4)
18. customThe oil was purified by radial chromatography

ORD record

ord-eae64075d72c4d7db615760bc9f03d1b

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153688B2