Ethyl 4-oxocyclohexanecarboxylate → HCID 89924053, compound

Temperature

-55 °C

5-Bromo-2-iodopyrimidine (5 g, 17.55 mmol) was dissolved in dry toluene (90 mL) and cooled to −50 to −60° C. in a dry ice/acetone bath. n-Butyllithium (2.5M solution in hexanes, 7.3 mL) was added dropwise, and the reaction mixture was aged for 20 minutes. A solution of ethyl 4-oxocyclohexanecarboxylate (2.99 g, 17.55 mmol) in toluene (10 mL) was added in one portion, and the reaction mixture was allowed to warm to r.t. and stirred for 30 minutes. The reaction mixture was quenched with water (50 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under vacuum. The resulting crude brown oil (6 g) was purified by chromatography on silica (Biotage, 100 g cartridge), eluting with a gradient of 0-50% ethyl acetate in heptanes, to afford a mixture of diastereoisomers of the title compound (2.99 g, 51%) as a yellow oil. Method C HPLC-MS: MH+ m/z 330, RT 1.32, 1.36 minutes.

1. temperatureto warm to r.t.
2. customThe reaction mixture was quenched with water (50 mL)
3. extractionextracted with EtOAc (2×100 mL)
4. washThe combined organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under vacuum
8. customThe resulting crude brown oil (6 g) was purified by chromatography on silica (Biotage, 100 g cartridge)
9. washeluting with a gradient of 0-50% ethyl acetate in heptanes
10. customto afford

ORD record

ord-885e2a6f382d4e0d8bb70ab168d6e36e

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309243B2