Diethyl Ether → HCID 86663032, compound

HRID 2410779Notes

Reaction equation

HRID 2410779 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][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.CCOC(C)=O.O>[N:1]([C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([CH:18]=[O:19])=[CH:14][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

8

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 86663031HCID 86663031, compound

Product 1

HCID 86663032HCID 86663032, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 3-amino-6-bromo-2-(4-(hydroxymethyl)phenyl)isonicotinate (5.7 g, 16.91 mmol) was dissolved in TFA (85 mL) and the solution was cooled in an ice bath. Sodium nitrite (2.57 g, 37 2 mmol) was added slowly with stirring to give a yellow solution with gas evolution. After 40 min, gas evolution had ceased and solid sodium azide (10.99 g, 169 mmol) was added in portions over about 5 min with gas evolution. Et2O (85 mL) was slowly added and a precipitate formed. After stirring for 0.5 hr, water was added and the mixture was extracted with EtOAc. The combined organic phases were washed with water (3×) and brine (1×) and then saturated Na2CO3 solution (until the aqueous phase was basic) and brine (1×). After drying the solvent with sodium sulfate, the solvent was removed. Flash chromatography (step gradient elution with DCM containing 40 to 0% hexane and then 10% EtOAc) afforded methyl 3-azido-6-bromo-2-(4-formylphenyl)isonicotinate (4.45 g, 12.3 mmol, 73% yield) as a fluffy yellow solid. 1H NMR (500 MHz, chloroform-d) δ ppm 10.10 (1H, s), 7.96-8.04 (2H, m), 7.90-7.96 (2H, m), 7.86 (1H, s), 4.03 (3H, s).

Workup

  1. temperaturethe solution was cooled in an ice bath
  2. customto give a yellow solution with gas evolution
  3. customa precipitate formed
  4. stirringAfter stirring for 0.5 hr
  5. extractionthe mixture was extracted with EtOAc
  6. washThe combined organic phases were washed with water (3×) and brine (1×)
  7. dry with materialAfter drying the solvent with sodium sulfate
  8. customthe solvent was removed
  9. washFlash chromatography (step gradient elution with DCM containing 40 to 0% hexane

Sources & evidence

ORD record
ord-4f2b94188aa4495ba2b55d62ec54fd06
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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