Diethyl Ether → Methyl 3-azido-6'-methoxy-6-(4-methoxyphenyl)-2,3'-bipyridine-4-carboxylate

HRID 2410686Notes

Reaction equation

HRID 2410686 reaction equation
[NH2:1][C:2]1[C:3]([C:20]2[CH:21]=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=2)=[N:4][C:5]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)=[CH:6][C:7]=1[C:8]([O:10][CH3:11])=[O:9].N([O-])=O.[Na+].[N-:32]=[N+:33]=[N-].[Na+].C(OCC)C>FC(F)(F)C(O)=O>[N:1]([C:2]1[C:3]([C:20]2[CH:21]=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=2)=[N:4][C:5]([C:12]2[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)=[CH:6][C:7]=1[C:8]([O:10][CH3:11])=[O:9])=[N+:32]=[N-:33]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 66604594Methyl 3-amino-6'-methoxy-6-(4-methoxyphenyl)-2,3'-bipyridine-4-carboxylate

Product 1

HCID 86663008Methyl 3-azido-6'-methoxy-6-(4-methoxyphenyl)-2,3'-bipyridine-4-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 3-amino-6′-methoxy-6-(4-methoxyphenyl)-2,3′-bipyridine-4-carboxylate (120 mg, 0.33 mmol) was dissolved in trifluoroacetic acid (1.6 mL) and the solution was cooled in an ice bath. Sodium nitrite (45 mg, 0.66 mmol) was added with stirring to give a dark red suspension. After 30 min, sodium azide (214 mg, 3.3 mmol) was added followed immediately by diethyl ether (1.6 mL). This was stirred in the ice bath for 30 min. and then partially concentrated on the rotary evaporator. The residue was partitioned between ethyl acetate and sufficient saturated aqueous sodium bicarbonate solution (gas evolution) to neutralize the mixture. The organic phase was separated, washed with brine, dried with sodium sulfate, and the solvent removed to leave methyl 3-azido-6′-methoxy-6-(4-methoxyphenyl)-2,3′-bipyridine-4-carboxylate (122 mg, 95% yield) as a yellow solid. MS (ESI) m/z 392.1 (M+H). 1H NMR (CDCl3) δ ppm 8.74 (1H, d, J=2.52 Hz), 8.13 (1H, dd, J=8.69, 2.39 Hz), 8.01 (2H, d, J=9.07 Hz), 7.98 (1H, s), 6.97 (2H, d, J=8.81 Hz), 6.85 (1H, d, J=8.81 Hz), 4.03 (3H, s), 4.01 (4H, s), 3.85 (3H, s).

Workup

  1. temperaturethe solution was cooled in an ice bath
  2. customto give a dark red suspension
  3. concentrationpartially concentrated on the rotary evaporator
  4. customThe residue was partitioned between ethyl acetate and sufficient saturated aqueous sodium bicarbonate solution (gas evolution)
  5. customThe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried with sodium sulfate
  8. customthe solvent removed

Sources & evidence

ORD record
ord-240ca224d2614425b0e6c3a884d2f6cb
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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