1,1'-Carbonyldiimidazole → Tert-butyl 4-(4-ethyl-3-iodophenyl)-4-methyl-3-oxopentanoic acid

Mono-tert-butyl malonic acid (72.5 g) was dissolved in DME (360 ml), added with TEA (189 ml) and magnesium chloride (29.63 g) and the mixture was stirred for 2 hrs. In a separate vessel, CDI (52.75 g) was added to the DME (360 ml) solution of 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid (90 g) and stirred at room temperature for 1 hr to prepare a solution. This solution was then added dropwise to the aforementioned mixture, and the resulting solution was washed with DME (90 ml) and stirred at 70° C. for 3 hrs. The reaction mixture was diluted with isopropyl acetate (225 ml) and heptane (225 ml), and the organic layer was washed with 2 N hydrochloric acid (684 ml), 0.17 N hydrochloric acid (540 ml), 15% aqueous solution of ammonium chloride (540 ml), 1 N aqueous solution of sodium hydroxide (540 ml) and 15% brine (540 ml) in order. The organic layer was concentrated under reduced pressure to obtain the title compound as a crude product, which was used for the next step without further purification.

1. stirringstirred at room temperature for 1 hr
2. customto prepare a solution
3. additionThis solution was then added dropwise to the aforementioned mixture
4. washthe resulting solution was washed with DME (90 ml)
5. stirringstirred at 70° C. for 3 hrs
6. additionThe reaction mixture was diluted with isopropyl acetate (225 ml) and heptane (225 ml)
7. washthe organic layer was washed with 2 N hydrochloric acid (684 ml), 0.17 N hydrochloric acid (540 ml), 15% aqueous solution of ammonium chloride (540 ml), 1 N aqueous solution of sodium hydroxide (540 ml) and 15% brine (540 ml) in order
8. concentrationThe organic layer was concentrated under reduced pressure

ORD record

ord-e37ff06774aa4b348f17057aff353ebb

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440922B2