Sodium Carbonate → 3-Dipropylamino-8-fluoro-5-(2-furyl)chroman

HRID 37668Notes

Reaction equation

HRID 37668 reaction equation
[CH2:1]([N:4]([CH2:23][CH2:24][CH3:25])[CH:5]1[CH2:14][C:13]2[C:8](=[C:9]([F:22])[CH:10]=[CH:11][C:12]=2S(C(F)(F)F)(=O)=O)[O:7][CH2:6]1)[CH2:2][CH3:3].[O:26]1[CH:30]=[CH:29][CH:28]=[C:27]1B(O)O.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C.C1(C)C=CC=CC=1>[CH2:1]([N:4]([CH2:23][CH2:24][CH3:25])[CH:5]1[CH2:14][C:13]2[C:8](=[C:9]([F:22])[CH:10]=[CH:11][C:12]=2[C:27]2[O:26][CH:30]=[CH:29][CH:28]=2)[O:7][CH2:6]1)[CH2:2][CH3:3]

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 2734357Furan-2-boronic acid2×HCID 190281873-Dipropylamino-8-fluoro-5-trifluoromethanesulfonylchroman

Product 1

HCID 190281363-Dipropylamino-8-fluoro-5-(2-furyl)chromanYield 52.9%

Reagents, catalysts & solvents 5

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 222AmmoniaSolventHCID 702EthanolSolvent2×HCID 1140TolueneSolvent

Procedure

In a three-necked round-bottom flask (25 mL) equipped with a magnetic stirrer and a reflux condensor the following reagents were mixed under nitrogen: 3-dipropylamino-8-fluoro-5-trifluoromethanesulfonylchroman (0.104 g; 0.25 mmol), absolute ethanol (1.7 mL), toluene (3.6 mL), 2-furylboronic acid (0.071 g; 0.64 mmol), lithium chloride (0.022 g; 0.51 mmol), 2M sodium carbonate (0.7 mL) and tetrakis(triphenylphosphine)palladium(0) (0.0073 g). The mixture was heated on an oil-bath to a reflux temperature (75°-80° C.). After 3 hours GC-analysis indicated a partial reaction (20% product and 66% starting material). Therefore more 2furylboronic acid (0.031 g; 0.28 mmol), absolute ethanol (0.2 mL) and tetrakis(triphenylphosphine)-palladium(0) (0.009 g) were added. The mixture was stirred at 75°-80° C. over night, then poured in 2M ammonia (40 mL) and extracted with ether (2×40 mL). The collected ether phases were dried (Na 2 SO4), filtered and concentrated in vacuo. The crude product was purified by flash-chromatography on a silica column with ethyl acetate/n-hexane (2:98). Relevant fractions were pooled and concentrated to give an oil consisting of impure product (72% GC). This material was purified in a second run by flash-chromatography on a silica column eluted with eluted with ethyl acetate/methylene chloride (1:99) to give 0.042 g (51% yield) of 3-dipropylamino-8-fluoro-5-(2-furyl)chroman as an oil.

Workup

  1. customIn a three-necked round-bottom flask (25 mL) equipped with a magnetic stirrer
  2. additiona reflux condensor the following reagents were mixed under nitrogen
  3. temperatureThe mixture was heated on an oil-bath to a reflux temperature (75°-80° C.)
  4. extractionextracted with ether (2×40 mL)
  5. dry with materialThe collected ether phases were dried (Na 2 SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash-chromatography on a silica column with ethyl acetate/n-hexane (2:98)
  9. concentrationconcentrated
  10. customto give an oil
  11. customThis material was purified in a second run by flash-chromatography on a silica column
  12. washeluted
  13. washwith eluted with ethyl acetate/methylene chloride (1:99)

Sources & evidence

ORD record
ord-acd63e9f39ff45bea58b4345433824e7
Source dataset
uspto-grants-1995_05
Patent number
US05420151

Reaction notes

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