Potassium Carbonate → HCID 86609120, compound

HRID 902331Notes

Reaction equation

HRID 902331 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@H:13]2[CH2:22][CH2:21][C:20]3[C:15](=[C:16](Br)[CH:17]=[C:18]([F:23])[CH:19]=3)[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@H:13]2[CH:22]=[CH:21][C:20]3[C:15](=[C:16]([C:30]4[CH:31]=[C:26]([Cl:25])[CH:27]=[CH:28][C:29]=4[Cl:32])[CH:17]=[C:18]([F:23])[CH:19]=3)[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27733712,5-Dichlorobenzeneboronic acidHCID 86609121HCID 86609121, compound

Product 1

HCID 86609120HCID 86609120, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 178424406HCID 178424406, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of [(R)-8-bromo-6-fluoro-3,4-dihydro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate, prepared in Example 38, step 2 (0.40 g, 0.97 mmol) and 2,5-dichlorophenylboronic acid (0.56 g, 2.9 mmol) in dioxane (10 ml) was added a solution of potassium carbonate (0.34 g, 2.4 mmol) in water (2 mL) and the mixture purged with nitrogen for 20 minutes. Dichlorobis(tri-o-tolylphosphine)palladium (II) (20 mg, 0.029 mmol) was added and the reaction mixture heated to reflux for 1 hour. The cooled reaction mixture was then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL). The organic layer was separated, washed with water (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford a yellow syrup. Purification by flash chromatography using a solvent gradient of 5 to 20% ethyl acetate in hexane gave 0.41 g (88%) of ((R)-8-(2,5-dichlorophenyl)-6-fluoro-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. MS (ES) m/z 496.0 ([M+NH4]+).

Workup

  1. customthe mixture purged with nitrogen for 20 minutes
  2. temperaturethe reaction mixture heated
  3. temperatureto reflux for 1 hour
  4. customThe cooled reaction mixture
  5. customwas then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL)
  6. customThe organic layer was separated
  7. washwashed with water (100 mL) and saturated brine (100 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto afford a yellow syrup
  12. customPurification by flash chromatography

Sources & evidence

ORD record
ord-ced208edd01648c6b437931d053ea4fd
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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