Ethyl bromodifluoroacetate → HCID 118093050, compound

HRID 2207425Notes

Reaction equation

HRID 2207425 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:20]=[CH:21][C:22]([CH:25]=[O:26])=[N:23][CH:24]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.Br[C:28]([F:35])([F:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30]>C1COCC1.[Zn]>[F:34][C:28]([F:35])([CH:25]([OH:26])[C:22]1[CH:21]=[CH:20][C:19]([C:4]2[CH:5]=[C:6]([NH:8][C:9]3[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=3)[CH:7]=[C:2]([CH3:1])[CH:3]=2)=[CH:24][N:23]=1)[C:29]([O:31][CH2:32][CH3:33])=[O:30]

Participants

5

Reactant 2

HCID 69585Ethyl bromodifluoroacetateHCID 131735917HCID 131735917, compound

Product 1

HCID 118093050HCID 118093050, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A flask fitted with a stirring bar was charged with zinc (64.9 mg, 0.992 mmol) and anhydrous THF (5.00 mL) under a nitrogen atmosphere. Then, a solution of 5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridine-2-carbaldehyde (250 mg, 0.698 mmol) in THF (5.00 mL) was added to the flask and the mixture was brought to reflux. Ethyl bromodifluoroacetate (135 μL, 1.048 mmol) was slowly added via syringe to the reaction mixture and refluxed for 1 hour. The reaction mixture was cooled to room temperature, quenched by the addition of saturated aqueous sodium thiosulfate (3.00 mL) and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (3:7 ethyl acetate:hexanes) to afford ethyl 2,2-difluoro-3-hydroxy-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propanoate. MS APCI C22H20F5N4O3 [M+H]+ 483. found 483. 1H NMR (500 MHz, CDCl3) δ 8.84 (d, J=1.7 Hz, 1H), 8.66 (d, J=4.8 Hz, 1H), 7.98 (dd, J=2.2 Hz, 8.1 Hz, 1H), 7.89 (s, 1H), 7.52 (d, J=9.1 Hz, 2H), 7.38 (s, 1H), 7.14 (s, 1H), 7.06 (d, J=4.9 Hz, 1H), 5.26 (dd, J=4.9 Hz, 17.5 Hz, 1H), 4.47-4.29 (m, 2H), 2.45 (s, 3H), 1.36 (t, J=7.1 Hz, 3H).

Workup

  1. customA flask fitted with a stirring bar
  2. temperatureto reflux
  3. temperaturerefluxed for 1 hour
  4. customquenched by the addition of saturated aqueous sodium thiosulfate (3.00 mL)
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography (3:7 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-0f3c47823bfb464da128febb78bf7e0f
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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