Pyridine → HCID 59529749, compound

HRID 1952381Notes

Reaction equation

HRID 1952381 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([Cl:19])[CH:18]=1)[O:5][C:6]1[C:7](C(O)=O)=[N:8][CH:9]=[CH:10][C:11]=1[Cl:12].C([N:22]([CH2:25]C)CC)C.N1C=CC=CC=1.[C:33]([OH:37])([CH3:36])([CH3:35])[CH3:34].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:45])=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([Cl:19])[CH:18]=1)[O:5][C:6]1[C:7]([NH:22][C:25](=[O:45])[O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[N:8][CH:9]=[CH:10][C:11]=1[Cl:12]

Participants

7

Reactant 5

HCID 1049PyridineHCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 59529731HCID 59529731, compound

Product 1

HCID 59529749HCID 59529749, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

3-(3-bromo-5-chlorophenoxy)-4-chloropyridine-2-carboxylic acid (1.29 g, 3.55 mmol) was suspended in toluene (10 mL) and the solvent evaporated in vacuo to azeotrope any residual water. This dried solid was dissolved in THF (10 mL) and cooled over an ice bath for 5 minutes. This solution was sequentially treated with triethylamine (719 ul, 7.11 mmol), pyridine (575 ul, 7.11 mmol), t-butanol (1.699 mL, 17.77 mmol) and lastly DPPA (1.151 mL, 5.33 mmol). This solution was allowed to stir at room temperature for 20 minutes and then heated to 65° C. for 60 minutes. This reaction mixture was allowed to cool to room temperature and then partitioned between ethyl acetate (2×100 mL) and saturated aqueous NaHCO3 (100 mL). The combined extracts were dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified by chromatography using silica gel (330 g) eluting with a gradient of 0-100% EtOAc in CH2Cl2 to give the title compound. LRMS (M+1): 334.6.

Workup

  1. customthe solvent evaporated in vacuo
  2. dissolutionThis dried solid was dissolved in THF (10 mL)
  3. temperaturecooled over an ice bath for 5 minutes
  4. temperatureheated to 65° C. for 60 minutes
  5. temperatureto cool to room temperature
  6. custompartitioned between ethyl acetate (2×100 mL) and saturated aqueous NaHCO3 (100 mL)
  7. dry with materialThe combined extracts were dried over MgSO4
  8. filtrationfiltered
  9. customthe solvent removed in vacuo
  10. customThe residue was purified by chromatography
  11. washeluting with a gradient of 0-100% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-e05cea2a675148698f5a1c2928a80fda
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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