Diethyl Ether → Methyl 3-azido-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate

HRID 2410757Notes

Reaction equation

HRID 2410757 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)=[N:10][C:9]([Br:26])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].[N-:31]=[N+:32]=[N-].[Na+].CCOCC>C(O)(C(F)(F)F)=O.O>[N:1]([C:2]1[C:11]([C:12]2[CH:13]=[CH:14][C:15]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:17]=2)=[N:10][C:9]([Br:26])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[N+:31]=[N-:32]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 86663009Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate

Product 1

HCID 86663025Methyl 3-azido-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinateYield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate (3.28 g, 7.94 mmol) was dissolved in TFA (40 mL) and the yellow solution was cooled in an ice bath. Solid sodium nitrite (1.1 g, 15.9 mmol) was added with stirring to give a red mixture with gas evolution. After 20 min, solid sodium azide (5.16 g, 79 mmol) was added over 5 min followed immediately by Et2O (40 mL). After 20 minutes water was added and the mixture was extracted with EtOAc. The combined organic phases were washed with water (3×), and saturated Na2CO3 solution (until the aqueous phase was basic) and brine. After drying the solvent with sodium sulfate, the solvent was removed. Flash chromatography (step gradient elution with hexane containing 10 to 40% DCM) afforded methyl 3-azido-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate (2.23 g, 5.08 mmol, 64% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 7.68-7.79 (3H, m), 7.29-7.49 (5H, m), 7.06 (2H, d, J=8.55 Hz), 4.00 (3H, s).

Workup

  1. temperaturethe yellow solution was cooled in an ice bath
  2. customto give a red mixture with gas evolution
  3. extractionthe mixture was extracted with EtOAc
  4. washThe combined organic phases were washed with water (3×), and saturated Na2CO3 solution (until the aqueous phase
  5. dry with materialAfter drying the solvent with sodium sulfate
  6. customthe solvent was removed
  7. washFlash chromatography (step gradient elution with hexane containing 10 to 40% DCM)

Sources & evidence

ORD record
ord-24b47a9b641647d1a208e082ba5b957f
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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