Ethyl bromodifluoroacetate → Ethyl 2-(4-bromo-2,6-dimethylphenyl)-2,2-difluoroacetate

HRID 708804

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5](I)=[C:6]([CH3:8])[CH:7]=1.Br[C:12]([F:19])([F:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14]>CS(C)=O.[Cu]>[Br:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5]([C:12]([F:19])([F:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:6]([CH3:8])[CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a degassed solution of 5-bromo-2-iodo-1,3-dimethylbenzene (3.9 g, 12.54 mmol) and ethyl 2-bromo-2,2-difluoroacetate (3.22 ml, 25.08 mmol) in DMSO (30 ml) was added copper (3.19 g, 50.2 mmol). The reaction mixture was stirred at 60° C. for 3 h, then cooled to r.t. and filtered. The filtrate was diluted with EtOAc and water, extracted with EtOAc (3×). The combined organic layer was washed with brine, dried with MgSO4, filtered and concentrated. The crude product was purified by flash chromatography to give Intermediate 7A (3.4 g, 11.07 mmol, 88% yield) as a colorless oil. 1H NMR (400 MHz, chloroform-d) δ ppm 1.32 (t, J=7.03 Hz, 3H) 2.44 (t, J=4.17 Hz, 6H) 4.32 (q, J=7.18 Hz, 2H) 7.23 (s, 2H). 19F NMR (376 MHz, chloroform-d) δ ppm −95.28 (br. s., 2F).

Workup

temperaturecooled to r.t.
filtrationfiltered
additionThe filtrate was diluted with EtOAc and water
extractionextracted with EtOAc (3×)
washThe combined organic layer was washed with brine
dry with materialdried with MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash chromatography

Sources & evidence

ORD record: ord-43108a86b60045159095cf0762cf1d8c
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174974B2

Linked notes

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