2,4-Difluoronitrobenzene → HCID 67382332, compound

LiHMDS (1 M solution in THF; 5.0 ml) was added slowly to an ice/ethanol-cooled solution of 3-methoxy-cyclohexanol (7:3 mixture of cis- and trans-isomers; 601 mg) in THF (8 ml). Cooling was suspended after 5 minutes and the mixture was stirred for 15 minutes at room temperature before addition of 2,4-difluoro-1-nitro-benzene (482 μl). After 4 h another 1.5 ml of LiHMDS (1 M solution in THF) was added and the reaction mixture was stirred over night at room temperature. The reaction mixture was quenched by addition of hydrochloric acid (0.1 M), diluted with ethyl acetate, and filtered through celite. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was submitted to column chromatography (silica gel, cyclohexane/ethyl acetate 85:15) to give the cis-isomer (650 mg) and the trans-isomer (230 mg).

1. temperatureCooling
2. customThe reaction mixture was quenched by addition of hydrochloric acid (0.1 M)
3. additiondiluted with ethyl acetate
4. filtrationfiltered through celite
5. washThe organic layer was washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. customto give the cis-isomer (650 mg)

ORD record

ord-f5ef169b325646d487f9dd2d0340ccc1

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754079B2