Ammonium Chloride → Tert-butyl (4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)carbamate

HRID 626540Notes

Reaction equation

HRID 626540 reaction equation
[N+:1]([C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:12]=2)=[CH:6][CH:5]=1)([O-])=O.[NH4+].[Cl-]>CO.C1COCC1.[Zn]>[NH2:1][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH:12]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 131735222Tert-butyl (4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)carbamate

Product 1

HCID 131735223Tert-butyl (4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)carbamateYield 110%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl (4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)carbamate (1.6 g, 4.81 mmol) in MeOH (25 mL) and THF (25 mL) was treated with NH4Cl (7.73 g, 144 mmol) followed by the portion-wise addition of zinc dust (3.15 g, 48.1 mmol) and stirred at RT overnight. The solids were removed via filtration through diatomaceous earth, washed with THF and EtOAc and the filtrate concentrated to dryness. The residue was suspended in THF, sonicated, the solids removed via filtration and the filtrate concentrated to dryness. The material was suspended in DCM, washed with water, the aqueous layer back-extracted with DCM and the combined organics were dried over Na2SO4 and concentrated to dryness to afford tert-butyl (4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)carbamate (1.6 g, 110%). 1H NMR (400 MHz, DMSO-d6): δ 9.76 (s, 1H), 8.06 (d, J=5.7 Hz, 1H), 7.78 (d, J=2.9 Hz, 1H), 7.26-7.25 (m, 2H), 6.55-6.48 (m, 2H), 6.01 (s, 2H), 1.40 (s, 9H); MS (ESI) m/z: 303.1 (M+H+).

Workup

  1. customThe solids were removed via filtration through diatomaceous earth
  2. washwashed with THF and EtOAc
  3. concentrationthe filtrate concentrated to dryness
  4. customsonicated
  5. customthe solids removed via filtration
  6. concentrationthe filtrate concentrated to dryness
  7. washwashed with water
  8. extractionthe aqueous layer back-extracted with DCM
  9. dry with materialthe combined organics were dried over Na2SO4
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-3da943d8659444a9821dab1d06235dc0
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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