p-Fluoronitrobenzene → HCID 58994995, compound

Temperature

-78 °C

To a solution of lithium diisopropylamide (12.2 mL, 22.0 mmol, 1.8 M) in 40 mL of THF at −78° C. was added tetrahydro-pyran-4-carboxylic acid methyl ester (2.88 g, 20.0 mmol) dropwise. The resulting mixture was stirred at −78° C. for 15 min, warmed to RT. 1,3-Dimethyl-tetrahydro-pyrimidin-2-one (2.69 g, 22.0 mmol) was added. The reaction was cooled to −78° C. again, 1-fluoro-4-nitro-benzene (3.10 g, 22.0 mmol) was added slowly. The resulting mixture was warmed to RT and stirred for 1 d under Ar. The reaction was treated with 30 mL of saturated NH4Cl and extracted with 80 mL of EtOAc. The organic extract was washed with H2O (50 mL), brine (20 mL), dried (Na2SO4) and concentrated. The residue was purified by flash chromatography on silica gel (5-20% EtOAc/hexane) to give 1.61 g (30%) of the title compound as a yellow solid. 1H-NMR (CDCl3; 400 MHz): δ 8.21 (d, 1H, J=9.0 Hz), 7.56 (d, 1H, J=9.0 Hz), 3.97 (m, 2H), 3.70 (s, 3H), 3.57 (m, 2H), 2.56 (m, 2H), 2.00 (m, 2H).

1. temperaturewarmed to RT
2. temperatureThe reaction was cooled to −78° C. again
3. temperatureThe resulting mixture was warmed to RT
4. stirringstirred for 1 d under Ar
5. extractionextracted with 80 mL of EtOAc
6. extractionThe organic extract
7. washwas washed with H2O (50 mL), brine (20 mL)
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography on silica gel (5-20% EtOAc/hexane)

ORD record

ord-b59c610e4bda4bed8753910ca3ca93e3

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859602B2