Water → HCID 67279257, compound

HRID 1842218Notes

Reaction equation

HRID 1842218 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13].[Cl-].[NH4+:15].[OH2:16].[O:17]1[CH2:21]CCC1.[C:22]1([CH3:28])[CH:27]=[CH:26][CH:25]=[CH:24]C=1>CCCCCC.C1(C)C=CC=CC=1.C(OCC)(=O)C>[NH2:15][C:28]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[F:13])[CH2:22][CH2:27][CH:26]([O:17][CH3:21])[CH:25]1[CH2:24][OH:16]

Participants

9

Reactant 5

HCID 962WaterHCID 25517Ammonium ChlorideHCID 612591-Bromo-2-fluorobenzeneHCID 22635083Tetrahydrofuran tolueneHCID 178418339Butyllithium

Product 1

HCID 67279257HCID 67279257, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of n-butyllithium in hexane (2.60 M; 7.07 mL) was added dropwise to a solution containing 2-bromofluorobenzene (2.09 mL) in tetrahydrofuran/toluene (3.36 mL/33.6 mL) under a nitrogen atmosphere at −78° C. The reaction solution was stirred at the same temperature for 10 minutes. A boron trifluoride-diethyl ether complex (2.27 mL) and a solution containing the compound obtained in Preparation Example 23-(7) (1.30 g) in toluene (10 mL) were added dropwise to the reaction solution at the same temperature. After stirring at the same temperature for 40 minutes, aqueous ammonium chloride was added to the reaction solution, followed by warming to room temperature. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was washed with a saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and the insoluble matter was separated by filtration. The filtrate was concentrated and the residue was dissolved in ethyl acetate-heptane. The solution was filtered through silica gel and concentrated. Acetic acid (31.0 mL) and zinc powder (5.02 g) were added at room temperature. The reaction solution was stirred at room temperature for four hours. The insoluble matter was separated by filtration through celite and the filtrate was concentrated. Ethyl acetate and a sodium bicarbonate solution were added to the residue, and the organic layer was separated. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The insoluble matter was separated by filtration and the filtrate was concentrated under reduced pressure to obtain the title compound (1.41 g).

Workup

  1. additionA boron trifluoride-diethyl ether complex (2.27 mL) and a solution containing the compound
  2. additionwere added dropwise to the reaction solution at the same temperature
  3. stirringAfter stirring at the same temperature for 40 minutes
  4. customthe organic layer was separated
  5. washThe organic layer was washed with a saturated sodium chloride solution
  6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  7. customthe insoluble matter was separated by filtration
  8. concentrationThe filtrate was concentrated
  9. dissolutionthe residue was dissolved in ethyl acetate-heptane
  10. filtrationThe solution was filtered through silica gel
  11. concentrationconcentrated
  12. additionAcetic acid (31.0 mL) and zinc powder (5.02 g) were added at room temperature
  13. stirringThe reaction solution was stirred at room temperature for four hours
  14. customThe insoluble matter was separated by filtration through celite
  15. concentrationthe filtrate was concentrated
  16. additionEthyl acetate and a sodium bicarbonate solution were added to the residue
  17. customthe organic layer was separated
  18. washThe organic layer was washed with saturated aqueous sodium chloride
  19. dry with materialdried over anhydrous magnesium sulfate
  20. customThe insoluble matter was separated by filtration
  21. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-4773c9cae1944429b4400d1c313926ea
Source dataset
uspto-grants-2015_02
Patent number
US08946210B2

Reaction notes

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