5-Bromo-2-iodopyridine → Rac-[2-(5-bromo-pyridin-2-yl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 384908

Reaction equation

HRID 384908 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[C:14]([O:18][C:19](=[O:36])[NH:20][CH:21]([C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=1)[C:22](=[O:27])N(OC)C)([CH3:17])([CH3:16])[CH3:15]>O1CCCC1>[C:14]([O:18][C:19](=[O:36])[NH:20][CH:21]([C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=1)[C:22]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1)=[O:27])([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 5936905-Bromo-2-iodopyridineHCID 87442373Rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester2×HCID 178418918HCID 178418918, compound

Product 1

HCID 68409891Rac-[2-(5-bromo-pyridin-2-yl)-1-(3,4-dichloro-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 0.705 g (2.41 mmol) 5-bromo-2-iodopyridine in 4.8 ml dry tetrahydrofuran were added at 0° C. drop-wise 1.20 ml (2.41 mmol) of a 2M solution of isopropylmagnesium chloride in tetrahydrofuran. The mixture was stirred at 0° C. for 1.5 h and then 0.250 g (0.688 mmol) rac-[(3,4-Dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) were added. The ice bath was removed and stirring continued at ambient temperature for 2 h. The reaction was quenched by addition of 7 ml saturated aqueous ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and evaporated. The crude product was purified by flash-chromatography over silica gel with a heptane/ethyl acetate gradient beginning with 5% ethyl acetate. The title compound was obtained al light yellow solid: MS (ISP): 459.1 and 461.1 (M+H)+, 403.0 and 405.1 ((M-isobutene)+H)+ (100%).

Workup

  1. customThe ice bath was removed
  2. stirringstirring
  3. waitcontinued at ambient temperature for 2 h
  4. customThe reaction was quenched by addition of 7 ml saturated aqueous ammonium chloride solution
  5. additionThe mixture was diluted with water
  6. extractionextracted with ethyl acetate
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by flash-chromatography over silica gel with a heptane/ethyl acetate gradient beginning with 5% ethyl acetate

Sources & evidence

ORD record
ord-9ed7ea5c01f644d98cf62c9452672e31
Source dataset
uspto-grants-2013_02
Patent number
US08367838B2

Linked notes

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