Diethyl Ether → Methyl 3-azido-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate

HRID 2410729Notes

Reaction equation

HRID 2410729 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([Cl:20])[CH:13]=2)=[N:10][C:9]([Br:21])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].[N-:26]=[N+:27]=[N-].[Na+].C(OCC)C>FC(F)(F)C(O)=O>[N:1]([C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([Cl:20])[CH:13]=2)=[N:10][C:9]([Br:21])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[N+:26]=[N-:27]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 86663013Methyl 3-amino-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate

Product 1

HCID 86663014Methyl 3-azido-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 3-amino-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate (181 mg, 0.487 mmol) was dissolved in trifluoroacetic acid (2.4 mL) and cooled in an ice bath. Solid sodium nitrite (67 mg, 0.97 mmol) was added with stirring to give a dark red mixture. After 10 minutes, solid sodium azide (317 mg, 4.87 mmol) was added followed by diethyl ether (2.4 mL). This was stirred in the ice bath for 10 minutes and then partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution) to neutralize the acid. The organic phase was separated, washed with brine, dried with sodium sulfate, and the solvent removed. The gave methyl 3-azido-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate (161 mg) as a yellow solid. MS (ESI) m/z 398.9 (M+H). 1H NMR (CDCl3) δ ppm 7.85 (1H, d, J=2.14 Hz), 7.75 (1H, s), 7.71 (1H, dd, J=8.55, 2.14 Hz), 7.01 (1H, d, J=8.55 Hz), 4.01 (3H, s), 3.96 (3H, s).

Workup

  1. temperaturecooled in an ice bath
  2. customto give a dark red mixture
  3. custompartitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution)
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried with sodium sulfate
  7. customthe solvent removed

Sources & evidence

ORD record
ord-1d3959e7e18f45a1bd0d283fbde8d73b
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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