Iodine → N-(4-Iodopyridin-3-yl)-2,2-dimethylpropanamide

HRID 1640905Notes

Reaction equation

HRID 1640905 reaction equation
N#N.[CH3:3][C:4]([CH3:15])([CH3:14])[C:5]([NH:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=1)=[O:6].NCCCCN.C([Li])CCC.[I:27]I.[NH4+].[Cl-]>C(OCC)(=O)C.C(OCC)C>[I:27][C:13]1[CH:12]=[CH:11][N:10]=[CH:9][C:8]=1[NH:7][C:5](=[O:6])[C:4]([CH3:15])([CH3:14])[CH3:3]

Participants

9

Reactant 6

HCID 807Iodine2×HCID 947NitrogenHCID 1045PutrescineHCID 25517Ammonium ChlorideHCID 46550442,2-dimethyl-N-(pyridin-3-yl)propanamideHCID 178418339Butyllithium

Product 1

HCID 10447729N-(4-Iodopyridin-3-yl)-2,2-dimethylpropanamideYield 23.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-68 °C

Procedure

Equip a 250-mL round bottom flask with a magnetic a stirrer, a thermocouple, a dry ice/acetone bath, a N2 atmosphere, and an addition funnel. Charge with 2,2-dimethyl-N-pyridin-3-yl-propionamide (3.0 g, 16.8 mmol), diethylether (67 mL), and tetramethylene diamine (4.68 g, 6.08 mL, 40.3 mmol). Cool the reaction to −78° C. Add slowly via glass syringe n-butyllithium (2.5 M solution in hexane, 16.2 mL, 40.3 mmol) over 10 min. Warm the reaction to −13° C. over 2 h. Cool the reaction to −78° C. Prepare an iodine solution (I2 8.5 g, 33.6 mmol in THF (20 mL)). Add the iodine solution to the reaction via the addition funnel and stir 2.5 h. at −68° C. Quench the reaction with the addition of a saturated NH4Cl solution (40 mL) and transfer into a separatory funnel. Add ethyl acetate (100 mL). Extract and discard the lower aqueous phase. Wash the organic layer with a saturated sodium thiosulfate solution (100 mL) and extract. Wash the organic phase with saturated aqueous sodium chloride and extract. Dry the organic phase over Na2SO4 and filter. Concentrate the product via rotary evaporation. Chromatograph on silica (80 g) eluting with gradient of 100% DCM to 70% ethyl acetate/30% DCM to afford 1.19 g (23%) of the title compound. MS (ES) m/z 306 [M+1]+.

Workup

  1. customEquip a 250-mL round bottom flask with a magnetic a stirrer
  2. temperatureCool
  3. customthe reaction to −78° C
  4. temperatureWarm
  5. customthe reaction to −13° C. over 2 h
  6. temperatureCool
  7. customthe reaction to −78° C
  8. customto the reaction via the addition funnel
  9. customQuench
  10. customthe reaction
  11. customtransfer into a separatory funnel
  12. extractionExtract
  13. washWash the organic layer with a saturated sodium thiosulfate solution (100 mL)
  14. extractionextract
  15. washWash the organic phase with saturated aqueous sodium chloride
  16. extractionextract
  17. dry with materialDry the organic phase over Na2SO4
  18. filtrationfilter
  19. concentrationConcentrate the product
  20. customvia rotary evaporation
  21. washChromatograph on silica (80 g) eluting with gradient of 100% DCM to 70% ethyl acetate/30% DCM

Sources & evidence

ORD record
ord-8911bd966ef44bd8b592a787a6dce8a3
Source dataset
uspto-grants-2012_02
Patent number
US08114872B2

Reaction notes

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