Diethyl Ether → HCID 86663037, compound

HRID 2410784Notes

Reaction equation

HRID 2410784 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][OH:19])[CH:13]=2)=[N:10][C:9]([Br:20])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].[N-:25]=[N+:26]=[N-].[Na+].CCOCC>C(O)(C(F)(F)F)=O.O>[N:1]([C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH:18]=[O:19])[CH:13]=2)=[N:10][C:9]([Br:20])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[N+:25]=[N-:26]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 86663036HCID 86663036, compound

Product 1

HCID 86663037HCID 86663037, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 3-amino-6-bromo-2-(3-(hydroxymethyl)phenyl)isonicotinate (1.35 g, 4.00 mmol) was dissolved in TFA (20 mL) and the yellow solution was cooled in an ice bath. Solid sodium nitrite (0.553 g, 8.01 mmol) was added with stirring to give a yellow solution with gas evolution. After 30 min, sodium azide (2.60 g, 40 0 mmol) was added over 5 min followed immediately by Et2O (20 mL). A precipitate formed and, after 0.5 hr, water was added and the mixture was extracted with EtOAc. The organic phases were washed with water (3×), brine (1×), and then saturated Na2CO3 solution (until the aqueous phase was basic) and brine (1×). After drying with sodium sulfate, the solvent was removed. Flash chromatography (step gradient elution with DCM containing 20% hexane, DCM and DCM containing 5% EtOAc) afforded methyl 3-azido-6-bromo-2-(3-formylphenyl)isonicotinate (0.90 g, 2.5 mmol, 63% yield) as a tan solid. 1H NMR (400 MHz, chloroform-d) δ ppm 10.09 (1H, s), 8.27 (1H, t, J=1.51 Hz), 8.01-8.07 (1H, m), 7.98 (1H, ddd, J=7.68, 1.51, 1.38 Hz), 7.84 (1H, s), 7.65 (1H, t, J=7.68 Hz), 4.02 (3H, s).

Workup

  1. temperaturethe yellow solution was cooled in an ice bath
  2. customto give a yellow solution with gas evolution
  3. customA precipitate formed and, after 0.5 hr
  4. extractionthe mixture was extracted with EtOAc
  5. washThe organic phases were washed with water (3×), brine (1×)
  6. dry with materialAfter drying with sodium sulfate
  7. customthe solvent was removed
  8. washFlash chromatography (step gradient elution with DCM containing 20% hexane, DCM and DCM containing 5% EtOAc)

Sources & evidence

ORD record
ord-52be28db5ce74760af18842220696c65
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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