Dimethylformamide → HCID 67608705, compound

HRID 1965209Notes

Reaction equation

HRID 1965209 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[F:8].[C:10]([O-:13])([O-])=O.[Cs+].[Cs+].[C:16]([O:20][C:21]([N:23]1[CH2:27][CH2:26][CH:25]2[NH:28][CH2:29][CH:30]([CH2:31]OS(C)(=O)=O)[CH:24]12)=[O:22])([CH3:19])([CH3:18])[CH3:17].CN([CH:40]=[O:41])C>CCOCC.O>[C:16]([O:20][C:21]([N:23]1[CH:24]2[CH:25]([N:28]([C:10]([O:41][CH2:40][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:13])[CH2:29][CH:30]2[CH2:31][O:9][C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=2)[CH2:26][CH2:27]1)=[O:22])([CH3:17])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 10796Cesium carbonateHCID 759273,4-DifluorophenolHCID 86665967HCID 86665967, compound

Product 1

HCID 67608705HCID 67608705, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of 3,4-difluoro-phenol (342 mg, 2.6 mmol) in DMF (5 mL) was treated with Cs2CO3 (1.0 g, 3.1 mmol). After 20 min, the yellow solution was treated with mesylate 79 (610 mg, 1.3 mmol) in DMF (5 mL). The reaction mixture was stirred at ambient temperature. After 16 h, the reaction mixture was heated at 60° C. for 3.5 h and then cooled to ambient temperature. The reaction mixture was diluted with Et2O and water. The layers were separated and the aqueous phase was extracted with Et2O. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by HPLC (2″ Dynamax® SiO2, 10% EtOAc/hexane to 100% EtOAc, 30 min; Flow: 40 mL/min) to afford the 78 (422 mg, 67%) as a light yellow-colored oil. 1H NMR (CDCl3, 300 MHz): δ7.37-7.28 (m, 5H), 7.05-7.03 (m, 1H), 6.66-6.64 (m, 1H), 6.54-6.51 (m, 1H), 5.18-5.09 (m, 2H), 4.49-4.47 (m, 1H), 4.24-4.16 (m, 1H), 3.99 (m, 0.5H), 3.81-3.69 (m, 3H), 3.62 (m, 0.5H), 3.55-3.49 (m, 1H), 3.25-3.16 (m, 1H), 2.87-2.74 (m, 1H), 2.26-2.12 (m, 1H), 1.99 (m, 1H), 1.49 (s, 9H) ppm.

Workup

  1. waitAfter 16 h
  2. temperaturethe reaction mixture was heated at 60° C. for 3.5 h
  3. temperaturecooled to ambient temperature
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with Et2O
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by HPLC (2″ Dynamax® SiO2, 10% EtOAc/hexane to 100% EtOAc, 30 min

Sources & evidence

ORD record
ord-d3b0226f8030458a8ca74cb41f381ecb
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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