1-Bromo-2-fluoro-4-iodobenzene → HCID 58938107, compound

HRID 2366476Notes

Reaction equation

HRID 2366476 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[F:9].C([Mg]Cl)(C)C.[C:15]([N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][C:23]1=[O:28])([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:23](=[O:28])[CH2:24][CH2:25][CH2:26][CH2:27][NH:22][C:15](=[O:16])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[CH:4][C:3]=1[F:9]

Participants

5

Reactant 3

HCID 27250061-Bromo-2-fluoro-4-iodobenzeneHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 58938107HCID 58938107, compoundYield 74.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-bromo-2-fluoro-4-iodobenzene (44.22 g, 0.147 mol) in tetrahydrofuran (160 mL) was added isopropylmagnesium chloride (2.0 M solution in tetrahydrofuran, 73.5 mL) at 0° C. and the mixture stirred at 0° C. for 3 hours. This solution was cannulated into a solution of 1-BOC-2-piperidone (24.4 g, 0.122 mol) in tetrahydrofuran (240 mL) at −78° C. and the mixture stirred at −78° C. for 1 hour. The solution was warmed to ambient temperature and stirred for one hour before quenching with water. Hydrochloric acid (2N, 120 mL) was added and the mixture stirred at ambient temperature for 10 minutes. The mixture was concentrated and the residue partitioned between ethyl acetate and brine. The organic layer was washed with brine, dried over magnesium sulfate and filtered. Concentration afforded the crude product which was recrystallized from hexane and dichloromethane to give 33.95 g of the title compound as a white solid. 1HNMR (CDCl3) δ 1.44 (s, 9H), 1.52-1.63 (m, 2H), 1.70-1.83 (m, 2H), 2.96 (t, J=7.1 Hz, 2H), 3.16 (q, J=6.4 Hz, 2H), 4.58 (s, 1H), 7.59-7.71 (m, 3H).

Workup

  1. stirringthe mixture stirred at −78° C. for 1 hour
  2. temperatureThe solution was warmed to ambient temperature
  3. stirringstirred for one hour
  4. custombefore quenching with water
  5. additionHydrochloric acid (2N, 120 mL) was added
  6. stirringthe mixture stirred at ambient temperature for 10 minutes
  7. concentrationThe mixture was concentrated
  8. customthe residue partitioned between ethyl acetate and brine
  9. washThe organic layer was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationConcentration
  13. customafforded the crude product which
  14. customwas recrystallized from hexane and dichloromethane

Sources & evidence

ORD record
ord-89c5f9a1241a41beafabd8b986714c2c
Source dataset
uspto-grants-2014_04
Patent number
US08697736B2

Reaction notes

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