Diethyl Ether → HCID 86663059, compound

HRID 2410836Notes

Reaction equation

HRID 2410836 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:14][CH:13]=2)=[N:10][C:9]([Br:24])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].[N-:29]=[N+:30]=[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][C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:14][CH:13]=2)=[N:10][C:9]([Br:24])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[N+:29]=[N-:30]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 86663058HCID 86663058, compound

Product 1

HCID 86663059HCID 86663059, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 3-amino-6-bromo-2-(4-morpholinophenyl)isonicotinate (2.0 g, 5.1 mmol) was quickly dissolved in TFA (25 mL) and the light brown solution was cooled in an ice-bath. Solid sodium nitrite (0.405 g, 5.86 mmol) was added in small portions over 5 min with stirring to give a dark red mixture. After 30 min, solid sodium azide (1.24 g, 19.1 mmol) was added over 1 min followed by Et2O (25 mL). The mixture was stirred in the ice-bath for 30 min. Water was added and the mixture was extracted with EtOAc. The combined organic phases were washed with water (3×), brine, sat. aq. NaHCO3 solution (until aq. phases were basic), and brine (1×). After drying with sodium sulfate, the solvent was removed and silica gel chromatography (step gradient elution with hexane containing 5, 10, 15, 20% EtOAc) to afford methyl 3-azido-6-bromo-2-(4-morpholinophenyl)isonicotinate (1.27 g, 3.04 mmol, 60% yield) as a solid. 1H NMR (500 MHz, chloroform-d) δ ppm 7.77 (2H, d, J=9.16 Hz), 7.70 (1H, s), 6.99 (2H, d, J=9.16 Hz), 4.02 (3H, s), 3.87-3.92 (4H, m), 3.26-3.31 (4H, m).

Workup

  1. temperaturethe light brown solution was cooled in an ice-bath
  2. customto give a dark red mixture
  3. extractionthe mixture was extracted with EtOAc
  4. washThe combined organic phases were washed with water (3×), brine, sat. aq. NaHCO3 solution (until aq. phases were basic), and brine (1×)
  5. dry with materialAfter drying with sodium sulfate
  6. customthe solvent was removed
  7. washsilica gel chromatography (step gradient elution with hexane containing 5, 10, 15, 20% EtOAc)

Sources & evidence

ORD record
ord-85f12df0fdab45da958e38c2dacbaacb
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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