2,6-Difluorobenzoyl chloride → (2,6-Difluorophenyl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)-methanone

HRID 422879Notes

Reaction equation

HRID 422879 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:13]=[CH:12][C:11]([Mg]Br)=[CH:10][CH:9]=1.[F:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:18]=1[C:19](Cl)=[O:20]>C1COCC1.[Zn+2].[Br-].[Br-]>[F:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:18]=1[C:19]([C:11]1[CH:12]=[CH:13][C:8]([O:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)=[CH:9][CH:10]=1)=[O:20]

Participants

5

Reactant 2

HCID 874382,6-Difluorobenzoyl chlorideHCID 178419637HCID 178419637, compound

Product 1

HCID 57701080(2,6-Difluorophenyl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)-methanone

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of ZnBr2 in THF (1.5 M, 2 mL, 3.0 mmol) was added to a solution of (4-(tetrahydro-2H-pyran-2-yloxy)phenyl)magnesium bromide in THF (0.2 M, 15 mL, 3 mmol) under an atmosphere of argon atr.t. The reaction mixture was stirred for 10 minutes, cooled with a dry-ice acetone bath. Palladium tetrakistriphenylphosphine (50 mg) and a solution of 2,6-difluorobenzoyl chloride (0.37 mL, 3 mmol) in THF (2 mL) were added. The mixture was stirred over night at r.t. The organic phase was washed with brine (2×20 mL), dried (Na2SO4) and concentrated yielding a solid. Purified by flash chromatography (eluent: heptane →20% ethyl acetate in heptane). Yield: 318 mg, 33% (approx. 85% pure according to 1H-NMR). 1H-NMR (400 MHz, CDCl3): δ 7.83-7.78 (m, 2H), 7.49-7.38 (m, 1H), 7.14-7.07 (m, 2H), 7.03-6.95 (m, 2H), 5.52 (t, J=3.1 Hz, 1H), 3.83-3.80 (m, 1H), 3.63-3.58 (m, 1H), 2.10-1.90 (m, 1H), 1.89-1.85 (m, 2H), 1.72-1.58 (m, 3H).

Workup

  1. temperaturecooled with a dry-ice acetone bath
  2. stirringThe mixture was stirred over night at r.t
  3. washThe organic phase was washed with brine (2×20 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customyielding a solid
  7. customPurified by flash chromatography (eluent: heptane →20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-43468f41c85e4d3b9e0db664bde69327
Source dataset
uspto-grants-2012_01
Patent number
US08101651B2

Reaction notes

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