Potassium Phosphate, Tribasic → tert-Butyl 2-(4-cyclopropyl-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate

Temperature

100 °C

In a microwave vial, tert-butyl 2-(4-bromo-5-oxo-2,5-dihydrofuran-3-yl)-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (90 mg, 0.22 mmol) was dissolved in toluene (2 mL) and water (0.2 mL). Potassium phosphate (138 mg, 0.650 mmol), tricyclohexylphosphine (18 mg, 0.065 mmol), cyclopropylboronic acid (74.5 mg, 0.867 mmol) and palladium acetate (4.87 mg, 0.022 mmol) were added. The reaction mixture was de-gassed and heated at 100° C. for 12 hours. After cooling to room temperature, the reaction mixture was concentrated and the resulting residue was dissolved in EtOAc (50 mL), washed with water (30 mL) and brine (30 mL), dried over sodium sulfate, and filtered. Removing the solvent gave crude product that was purified by column chromatography eluting with 0-100% EtOAc/hexane gradient to yield the title compound. 1H NMR (500 MHz, CDCl3) δ 5.20 (s, 2H), 4.22 (m, 2H), 3.99 (m, 2H), 3.05 (m, 2H), 2.09 (m, 2H), 1.92 (m, 2H), 1.60 (m, 2H), 1.56 (m, 10H), 1.02 (m, 2H), 0.82 (m, 2H).

1. customThe reaction mixture was de-gassed
2. temperatureAfter cooling to room temperature
3. concentrationthe reaction mixture was concentrated
4. dissolutionthe resulting residue was dissolved in EtOAc (50 mL)
5. washwashed with water (30 mL) and brine (30 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. customRemoving the solvent
9. customgave crude product that
10. customwas purified by column chromatography
11. washeluting with 0-100% EtOAc/hexane gradient

ORD record

ord-1ed48d9f5b4043b08fc6dce16996da41

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952166B2