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Diethyl Ether → Methyl 3-azido-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate

HRID 2410740
Notes
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Reaction equation

HRID 2410740 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([O:20][CH3:21])=[O:19])=[CH:14][CH:13]=2)=[N:10][C:9]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([F:30])[CH:23]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].[N-:35]=[N+:36]=[N-].[Na+].C(OCC)C>FC(F)(F)C(O)=O>[N:1]([C:2]1[C:11]([C:12]2[CH:13]=[CH:14][C:15]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:17]=2)=[N:10][C:9]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([F:30])[CH:23]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[N+:35]=[N-:36]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 66604696Methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate

Product 1

HCID 86663018Methyl 3-azido-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinateYield 99.5%

Reagents, catalysts & solvents

1
HCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)-isonicotinate (1.00 g, 2.44 mmol) was dissolved in trifluoroacetic acid (12 mL) and the yellow solution was cooled in an ice bath. Powdered sodium nitrite (0.336 gm, 4.87 mmol) was added with stirring to give a dark red mixture. After 30 min, powdered sodium azide (1.59 g, 24.4 mmol) was added followed by diethyl ether (12 mL). The light red mixture was stirred in the ice bath for 30 min. The reaction was partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution) to neutralize the acid. The organic phase was washed with brine, dried with sodium sulfate, and the solvent removed. Flash silica gel chromatography (elution with a 1:1 mixture of methylene chloride and EtOAc) afforded methyl 3-azido-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate (1.06 gm). 1H NMR (CDCl3) δ ppm 8.17 (2H, d, J=7.93 Hz), 8.01 (1H, s), 7.91 (2H, d, J=7.93 Hz), 7.82-7.88 (1H, m), 7.79 (1H, d, J=8.55 Hz), 7.04 (1H, t, J=8.55 Hz), 4.05 (3H, s), 3.96 (3H, s), 3.94 (3H, s).

Workup

  1. temperaturethe yellow solution was cooled in an ice bath
  2. customto give a dark red mixture
  3. customThe reaction was partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution)
  4. washThe organic phase was washed with brine
  5. dry with materialdried with sodium sulfate
  6. customthe solvent removed
  7. washFlash silica gel chromatography (elution
  8. additionwith a 1:1 mixture of methylene chloride and EtOAc)

Sources & evidence

ORD record
ord-d72d954cbb17401db96de4beba57a824
Source dataset
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08815840B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes