Diethyl Ether → (4-Fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

HRID 1993622Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:5]=[C:4]([F:15])[CH:3]=1.[Li]CCCC.[F:21][C:22]1[CH:29]=[CH:28][C:25]([C:26]#N)=[CH:24][C:23]=1[O:30][CH3:31].CC[O:34]CC>C1COCC1>[F:21][C:22]1[CH:29]=[CH:28][C:25]([C:26]([C:2]2[CH:7]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:5]=[C:4]([F:15])[CH:3]=2)=[O:34])=[CH:24][C:23]=1[O:30][CH3:31]

Participants

Conditions

Temperature: -60 °C

Procedure

To a solution of 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (15 g, 51.7 mmol) in Et2O (100 mL) was added n-BuLi (20.7 mL, 2.5 M, 51.7 mmol) at −75° C. The reaction mixture was allowed to warm up to −60° C., followed by the addition of 4-fluoro-3-methoxy-benzonitrile (7.5 g, 46.6 mmol) in a mixture of THF and Et2O (6 mL/6 mL). The reaction was quenched immediately by addition of H2O. The aqueous portion was extracted with Et2O. The separated organic portion was washed by 1N HCl, concentrated under reduced pressure and purified by ISCO chromatography using hexanes/EtOAc (0-10%) to afford (4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as white powder (13 g, 71%). LCMS: RT=4.101 min, [M+H] 345.1 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm)

Workup

customThe reaction was quenched immediately by addition of H2O
extractionThe aqueous portion was extracted with Et2O
washThe separated organic portion was washed by 1N HCl
concentrationconcentrated under reduced pressure
custompurified by ISCO chromatography

Sources & evidence

ORD record: ord-554c5cc793bd49a4959e065732e1217b
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652023B2

Reaction notes

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