Triethylamine → 2-(Azetidin-1-ylcarbonyl)-5-bromopyridine

HRID 600556Notes

Reaction equation

HRID 600556 reaction equation
C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]([OH:16])=O)=[N:12][CH:13]=1.O1CCOCC1.Cl.[NH:24]1[CH2:27][CH2:26][CH2:25]1.C(N(CC)CC)C>CN(C=O)C.Cl.C(Cl)Cl>[N:24]1([C:14]([C:11]2[CH:10]=[CH:9][C:8]([Br:7])=[CH:13][N:12]=2)=[O:16])[CH2:27][CH2:26][CH2:25]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 312751,4-DioxaneHCID 65578Oxalyl chlorideHCID 6085445-Bromopyridine-2-carboxylic acidHCID 12308726Azetidine hydrochloride

Product 1

HCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridineYield 65%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (11.5 mL, 130 mmol) then DMF (2 drops) were added to a mixture of 5-bromopyridine-2-carboxylic acid (CAS no. 30766-11-1) (12.6 g, 62.4 mmol) in 4M HCl in dioxane (15.6 mL, 74.9 mmol) and DCM (300 mL). The mixture was stirred at ambient temperature for 18 hours. The volatiles were removed under reduced pressure and azeotroped with toluene. The residue was dissolved in DCM (300 mL). Azetidine hydrochloride (6.14 g, 65.5 mmol) then triethylamine (24 mL, 187 mmol) were added and the mixture stirred at ambient temperature for 20 hours. The mixture was concentrated under reduced pressure and ethyl acetate (400 mL) added to the residue. The resulting mixture was washed with water (100 mL), filtered, washed with 1M citric acid solution (50 mL), saturated sodium bicarbonate solution (50 mL) and brine (50 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography, eluting with a gradient of 0-40% ethyl acetate in isohexane to afford the product (8.8 g, 65%). m/z 242 (M+H)+.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customazeotroped with toluene
  3. dissolutionThe residue was dissolved in DCM (300 mL)
  4. stirringthe mixture stirred at ambient temperature for 20 hours
  5. concentrationThe mixture was concentrated under reduced pressure and ethyl acetate (400 mL)
  6. additionadded to the residue
  7. washThe resulting mixture was washed with water (100 mL)
  8. filtrationfiltered
  9. washwashed with 1M citric acid solution (50 mL), saturated sodium bicarbonate solution (50 mL) and brine (50 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customthe solvent removed under reduced pressure
  13. customThe residue was purified by flash chromatography
  14. washeluting with a gradient of 0-40% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-4d0296ae03974dddbf18f0f5ed8fa0e9
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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