Diethyl Ether → Methyl 3-azido-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate

HRID 2410866Notes

Reaction equation

HRID 2410866 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)(=[O:20])=[O:19])=[CH:14][CH:13]=2)=[N:10][C:9]([Br:27])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].[N-:32]=[N+:33]=[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]([S:18]([N:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)(=[O:19])=[O:20])=[CH:16][CH:17]=2)=[N:10][C:9]([Br:27])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[N+:32]=[N-:33]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 86663067Methyl 3-amino-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate

Product 1

HCID 86663068Methyl 3-azido-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinateYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 3-amino-6-bromo-2-(4-(morpholinosulfonyl)phenyl)-isonicotinate (0.988 g, 2.17 mmol) was dissolved in TFA (11 mL) and the yellow solution was cooled in an ice bath. Powdered sodium nitrite (0.299 g, 4.33 mmol) was added with stirring to give a dark red mixture with gas evolution. After 20 min, powdered sodium azide (1.41 g, 21.7 mmol) was added over 5 min followed by Et2O (11 mL). A thick precipitate formed and, after 30 min, water was added and the mixture was extracted with EtOAc. The organic phase was washed with water (3×), brine (1×), saturated aqueous Na2CO3 solution (so that the aqueous phase was basic), and brine. After drying the solvent with sodium sulfate, the solvent was removed and silica gel chromatography (step gradient elution with DCM containing 0 to 10% EtOAc) afforded methyl 3-azido-6-bromo-2-(4-(morpholinosulfonyl)phenyl)isonicotinate (918 mg, 1.90 mmol, 88% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 7.93-7.96 (2H, m), 7.87 (1H, s), 7.85 (2H, d, J=8.24 Hz), 4.03 (3H, s), 3.73-3.77 (4H, m), 3.03-3.07 (4H, m).

Workup

  1. temperaturethe yellow solution was cooled in an ice bath
  2. customto give a dark red mixture with gas evolution
  3. customA thick precipitate formed and, after 30 min
  4. extractionthe mixture was extracted with EtOAc
  5. washThe organic phase was washed with water (3×), brine (1×), saturated aqueous Na2CO3 solution (so that the aqueous phase
  6. dry with materialAfter drying the solvent with sodium sulfate
  7. customthe solvent was removed
  8. washsilica gel chromatography (step gradient elution with DCM containing 0 to 10% EtOAc)

Sources & evidence

ORD record
ord-afbcf43adcc34cbf839c97e1377aad6f
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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