Water → Methyl p-toluenesulfonate

HRID 902317Notes

Reaction equation

HRID 902317 reaction equation
BrC1C=C(F)C=C2C=1O[C@@H]([CH2:12][O:13][S:14]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)(=[O:16])=[O:15])C=C2.COC1C=CC=CC=1B(O)O.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.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>[CH3:23][C:20]1[CH:21]=[CH:22][C:17]([S:14]([O:13][CH3:12])(=[O:16])=[O:15])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 86609111(R)-(8-bromo-6-fluoro-2H-chromen-2-yl)methyl-4-methylbenzenesulfonate

Product 1

HCID 6645Methyl p-toluenesulfonate

Reagents, catalysts & solvents 2

HCID 178424406HCID 178424406, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-(8-bromo-6-fluoro-2H-chromen-2-yl)methyl-4-methylbenzenesulfonate (0.40 g, 0.97 mmol) and 2-methoxyphenylboronic acid (0.44 g, 2.9 mmol) in dioxane (10 mL) was added potassium carbonate (0.33 g, 2.4 mmol), dichlorobis(tri-o-tolylphosphine)palladium (II) (23 mg, 0.029 mmol) and water (2 mL). The reaction mixture was heated to reflux for 2 hours. 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. Purification by flash chromatography using a solvent gradient of 0 to 20% ethyl acetate in hexane gave 0.46 g (100%) of(R)-6-fluoro-8-(2-methoxyphenyl)-2H-chromen-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. MS (ES) m/z 441.0 ([M+H]+).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. customThe cooled reaction mixture
  4. customwas then partitioned between ethyl acetate (100 mL) and 2.0 M aqueous sodium hydroxide (100 mL)
  5. customThe organic layer was separated
  6. washwashed with water (100 mL) and saturated brine (100 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-246b0ffe5e0f41d39d80f2a770bfc7b5
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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