Ethyl bromodifluoroacetate → Ethyl 2-(4-(4-(2-ethoxy-2-oxoethyl)phenyl)pyridin-2-yl)-2,2-difluoroacetate

HRID 592228Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.Br[C:21]([F:28])([F:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>CN(C=O)C>[CH2:18]([O:17][C:15](=[O:16])[CH2:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:21]([F:28])([F:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:7]=2)=[CH:9][CH:10]=1)[CH3:19]

Participants

Conditions

Temperature: 80 °C

Procedure

To a sealed tube were added ethyl 2-(4-(2-bromopyridin-4-yl)phenyl)acetate 203-3 (440 mg, 1.37 mmol), ethyl 2-bromo-2,2-difluoroacetate (1.7 mL, 13.7 mmol), Cu (1.3 g, 20.6 mmol) and DMF (5 mL). The reaction mixture was bubbled with nitrogen for 1 minute and stirred at 80° C. for 1 hour. After cooling to room temperature, the mixture was filtered through a layer of Celite and concentrated. The residue was purified by silica gel flash chromatography and eluted with 20% ethyl acetate in hexane to give ethyl 2-(4-(4-(2-ethoxy-2-oxoethyl)phenyl)pyridin-2-yl)-2,2-difluoroacetate 203-4. MS m/z 364.2 (M+1).

Workup

customThe reaction mixture was bubbled with nitrogen for 1 minute
temperatureAfter cooling to room temperature
filtrationthe mixture was filtered through a layer of Celite
concentrationconcentrated
customThe residue was purified by silica gel flash chromatography
washeluted with 20% ethyl acetate in hexane

Sources & evidence

ORD record: ord-29947b1debe444fbb21dd0d5b407390e
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238646B2

Reaction notes

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