1,4-Dioxane → Methyl 2'-fluoro-5'-(methyloxy)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,1'-biphenyl-4-carboxylate

HRID 1662449Notes

Reaction equation

HRID 1662449 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][C:11]=1I.O1CCOCC1.[CH3:27][C:28]1([CH3:35])[C:32]([CH3:34])([CH3:33])[O:31][BH:30][O:29]1>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][C:11]=1[B:30]1[O:31][C:32]([CH3:34])([CH3:33])[C:28]([CH3:35])([CH3:27])[O:29]1

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 57705628Methyl 2'-fluoro-2-iodo-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

Product 1

HCID 57706776Methyl 2'-fluoro-5'-(methyloxy)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,1'-biphenyl-4-carboxylateYield 52.4%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A screw-cap vial was charged with 66.15D (2.08 g, 5.39 mmol), 1,4-dioxane (20 mL), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) DCM adduct (available from Strem) (0.220 g, 0.269 mmol). The suspension was sparged with N2, and to it were added TEA (2.25 mL, 16.2 mmol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (available from Aldrich) (1.17 mL, 8.08 mmol). The resulting mixture was stirred overnight at 100° C. (sealed vial), cooled to room temperature, diluted with water, and extracted with EtOAc. The combined organic layers were washed with water, 1 N HCl, and brine, dried (MgSO4), and concentrated. The crude product was twice purified by silica gel flash chromatography (0-15% EtOAc/hexane) to afford 66.56A (1.09 g, 52% yield) as a crystalline white solid.

Workup

  1. customThe suspension was sparged with N2
  2. custom(sealed vial)
  3. temperaturecooled to room temperature
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with water, 1 N HCl, and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude product was twice purified by silica gel flash chromatography (0-15% EtOAc/hexane)

Sources & evidence

ORD record
ord-488b4efa4777487babe376d11021019a
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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