Hydrochloric Acid → 2-[2-(4-morpholin-3-ylphenyl)-2H-tetrazol-5-yl]pyridine

HRID 734258Notes

Reaction equation

HRID 734258 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[N:12]=[N:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[N:9]2)=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+].[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1.Cl>C1COCC1.CCOCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH:50]1[CH2:55][CH2:54][O:53][CH2:52][CH:51]1[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[N:12]=[N:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[N:9]2)=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 686178672-[2-(4-bromophenyl)-2H-tetrazol-5-yl]pyridine

Product 1

HCID 686181552-[2-(4-morpholin-3-ylphenyl)-2H-tetrazol-5-yl]pyridine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a flask containing 2-[2-(4-bromophenyl)-2H-tetrazol-5-yl]pyridine (150 mg, 0.5 mmol), tris(dibenzylideneacetone)dipalladium(0) (26 mg, 0.025 mmol), 2-(dicyclohexylphosphino)biphenyl (18 mg, 0.05 mmol), and sodium t-butoxide (67 mg, 0.7 mmol), degassed toluene was added and the resulting mixture was stirred under nitrogen until homogeneity. Morpholine (53 μL, 0.6 mmol) was added to the mixture via syringe, and the reaction was heated to 80° C. The solution was then stirred for 18 h under nitrogen. The reaction mixture was quenched with water (20 mL), extracted with EtOAc (3×20 mL), and washed with brine. The organic phase was dried over Na2SO4 and concentrated in vacuo. The crude residue was chromatographed on silica gel eluting with 40% EtOAc in hexanes to afford a yellow solid. This was dissolved in anhydrous THF (10 mL) and HCl (1.5equiv) in ether was added, the precipitate was filtered to afford 2-[2-(4-morpholin-3-ylphenyl)-2H-tetrazol-5-yl]pyridine as a yellow solid. 1H NMR ((CD3)2SO, 300 MHz) δ 8.82 (d, 1H), 8.28 (d, 1H), 8.08 (dt, 1H), 7.51-7.68 (m, 4H), 7.23 (m, 1H), 3.77 (m, 4H), 3.25 (m, 4H). MS (ESI) MS 309 (M+H)+.

Workup

  1. customdegassed toluene
  2. additionwas added
  3. stirringThe solution was then stirred for 18 h under nitrogen
  4. customThe reaction mixture was quenched with water (20 mL)
  5. extractionextracted with EtOAc (3×20 mL)
  6. washwashed with brine
  7. dry with materialThe organic phase was dried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was chromatographed on silica gel eluting with 40% EtOAc in hexanes
  10. customto afford a yellow solid
  11. filtrationthe precipitate was filtered

Sources & evidence

ORD record
ord-38fcb422edb14a018fd56e2ee5e9cf80
Source dataset
uspto-grants-2009_09
Patent number
US07592337B2

Reaction notes

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