(1,1'-Biphenyl)-2-ol → HCID 66845232, compound

HRID 1480581Notes

Reaction equation

HRID 1480581 reaction equation
[C:1]1(C2C=CC=CC=2O)C=CC=C[CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:20]([O:26][CH2:27][CH3:28])(=[O:25])[CH2:21][C:22]([O-:24])=[O:23].[Cl:29][C:30]1[CH:35]=[C:34]([F:36])[C:33](I)=[CH:32][C:31]=1[F:38].O1CCCC1>[NH4+].[Cl-].CCOC(C)=O.[Cu]I>[Cl:29][C:30]1[C:31]([F:38])=[CH:32][C:33]([CH:21]([C:22]([O:24][CH2:1][CH3:2])=[O:23])[C:20]([O:26][CH2:27][CH3:28])=[O:25])=[C:34]([F:36])[CH:35]=1

Participants

9

Reactant 5

HCID 7017(1,1'-Biphenyl)-2-olHCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 3595298Propanedioic acid, monoethyl esterHCID 510000881-Chloro-2,5-difluoro-4-iodobenzene

Product 1

HCID 66845232HCID 66845232, compoundYield 388.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
90 °C

Procedure

Copper(I) iodide (69.4 mg, 0.364 mmol), 2-phenylphenol (93.0 mg, 0.546 mmol) and cesium carbonate (1.78 g, 5.46 mmol) were added to a dry flask under nitrogen. Ethyl malonate (1.11 mL, 7.29 mmol) was added to the mixture, followed by 1-chloro-2,5-difluoro-4-iodobenzene (1.00 g, 3.64 mmol) in tetrahydrofuran (3.64 mL, 44.9 mmol). The reaction mixture was sealed and heated to 90° C. After 12 hours, the reaction mixture was allowed to cool to room temperature and then diluted with saturated NH4Cl and EtOAc. The organic layer was separated, dried and filtered through Celite. The brown oil was purified via silica gel chromatography (0-30% EtOAc-hexane) to give diethyl 2-(4-chloro-2,5-difluorophenyl)malonate (0.65 g, 58%). 1H NMR (400 MHz, CDCl3) δ 7.37 (dd, J=6.3, 9.3, 1H), 7.17 (dd, J=6.1, 8.9, 1H), 4.91 (s, 1H), 4.33-4.14 (m, 4H), 1.28 (t, J=7.2, 6H).

Workup

  1. customThe reaction mixture was sealed
  2. temperatureto cool to room temperature
  3. customThe organic layer was separated
  4. customdried
  5. filtrationfiltered through Celite
  6. customThe brown oil was purified via silica gel chromatography (0-30% EtOAc-hexane)

Sources & evidence

ORD record
ord-03aad915c45c49e49c526ef2c309e37e
Source dataset
uspto-grants-2016_08
Patent number
US09409886B2

Reaction notes

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