Sodium Azide → HCID 86663066, compound

HRID 2410861Notes

Reaction equation

HRID 2410861 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][CH:31]([CH3:34])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.N([O-])=O.[Na+].[N-:39]=[N+:40]=[N-].[Na+]>Cl.O>[N:1]([C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:19])([F:20])[F:21])[CH:13]=2)=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][CH:31]([CH3:34])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1)=[N+:39]=[N-:40]

Participants

6

Reactant 3

HCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 66605237HCID 66605237, compound

Product 1

HCID 86663066HCID 86663066, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×

Procedure

A mixture of methyl 4′-amino-4″-(4-methylpiperidin-1-yl)-3-trifluoromethyl-[1,1′:3′,1″-terphenyl]-5′-carboxylate (250 mg, 0.532 mmol) in hydrochloric acid, (12 mL, 37% aqueous solution) was cooled in an ice bath and a solution of sodium nitrite (220 mg, 3.19 mmol) in water (2 mL) was added slowly. The orange-red solution was stirred for 30 min and a solution of sodium azide (208 mg, 3.19 mmol) in water (2 mL) was added dropwise. After 30 min this was partitioned between DCM and water. The organic phase washed with water and the combined organic phases were basified with 10 N aq. NaOH solution. This was extracted with DCM and the organic phases were washed with sat. NaHCO3 solution, brine, and dried with sodium sulfate. Removal of the solvent followed by silica gel chromatography (step gradient elution with DCM containing 0 to 2% MeOH) afford methyl 4′-azido-4″-(4-methylpiperidin-1-yl)-3-trifluoromethyl-[1,1′:3′,1″-terphenyl]-5′-carboxylate (128 mg, 0.26 mmol, 49% yield) as a solid. 1H NMR (500 MHz, chloroform-d) δ ppm 8.02 (1H, d, J=2.44 Hz), 7.85 (1H, s), 7.79 (1H, d, J=7.63 Hz), 7.68 (1H, d, J=2.44 Hz), 7.64 (1H, d, J=7.63 Hz), 7.59 (1H, d, J=7.63 Hz), 7.42 (2H, d, J=8.55 Hz), 7.04 (2H, d, J=8.85 Hz), 4.03 (3H, s), 3.26-3.39 (4H, m), 2.57-2.69 (4H, m), 2.38 (3H, s).

Workup

  1. temperaturewas cooled in an ice bath
  2. customAfter 30 min this was partitioned between DCM and water
  3. washThe organic phase washed with water
  4. extractionThis was extracted with DCM
  5. washthe organic phases were washed with sat. NaHCO3 solution, brine
  6. dry with materialdried with sodium sulfate
  7. customRemoval of the solvent
  8. washfollowed by silica gel chromatography (step gradient elution with DCM containing 0 to 2% MeOH)

Sources & evidence

ORD record
ord-d14ec6cf6a4546d9869b18bc730d36f4
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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