Azidomethyl 2,2-dimethylpropanoate → (4-(4-(4-amino-3-fluorophenoxy)pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl pivalate

HRID 450476Notes

Reaction equation

HRID 450476 reaction equation
[C:1]([O:7][CH2:8][N:9]=[N+:10]=[N-:11])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[C:12]([C:14]1[CH:19]=[C:18]([O:20][C:21]2[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([F:28])[CH:22]=2)[CH:17]=[CH:16][N:15]=1)#[CH:13].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>C(O)(C)(C)C.O.CCOC(C)=O.S([O-])([O-])(=O)=O.[Cu+2]>[C:1]([O:7][CH2:8][N:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[C:18]([O:20][C:21]3[CH:26]=[CH:25][C:24]([NH2:27])=[C:23]([F:28])[CH:22]=3)[CH:17]=[CH:16][N:15]=2)[N:11]=[N:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

8

Reactant 3

HCID 11521126Azidomethyl 2,2-dimethylpropanoateHCID 23667548Sodium AscorbateHCID 598255834-(2-Ethynylpyridin-4-yloxy)-2-fluorobenzenamine

Product 1

HCID 67399290(4-(4-(4-amino-3-fluorophenoxy)pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl pivalateYield 90%

Reagents, catalysts & solvents 4

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent3×HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of azidomethyl pivalate (0.075 g, 0.477 mmol), 4-(2-ethynylpyridin-4-yloxy)-2-fluorobenzenamine from Example A21 (0.109 g, 0.477 mmol) in t-butanol (0.6 mL) and water (0.6 mL) was added sodium ascorbate (0.021 g, 0.095 mmol). Copper(II)sulfate in water (0.048 ml, 0.048 mmol) was added to the above suspension and the dark red mixture was stirred for 3 h at RT. It was diluted with water (30 mL) and EtOAc (20 mL), the layers were separated and the aqueous layer was extracted with EtOAc (2×15 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated to afford (4-(4-(4-amino-3-fluorophenoxy)pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl pivalate as a red solid. (0.165 g, 90% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.54 (s, 1H), 8.46 (brs, 1H), 7.60 (s, 1H), 6.98 (d, J=8.8 Hz, 1H), 6.94 (d, J=3.6 Hz, 1H), 6.83-6.81 (m, 2H), 6.42 (s, 2H), 4.78 (s, 2H), 1.17 (s, 9H); MS (ESI) m/z: 386.1 (M+H+).

Workup

  1. customthe layers were separated
  2. extractionthe aqueous layer was extracted with EtOAc (2×15 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ef1b22eed3784c7fabd77a100bf2b7f1
Source dataset
uspto-grants-2013_07
Patent number
US08486951B2

Reaction notes

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