tert-Butanol → 1-Methyl-5-phenoxy-1H-pyrazol-4-ylamine

HRID 1778198Notes

Reaction equation

HRID 1778198 reaction equation
[CH3:1][N:2]1[C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:5](C(O)=O)[CH:4]=[N:3]1.CC(O)(C)C.CC[N:24](C(C)C)C(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>O1CCOCC1>[CH3:1][N:2]1[C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:5]([NH2:24])[CH:4]=[N:3]1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 84016145HCID 84016145, compound

Product 1

HCID 867185511-Methyl-5-phenoxy-1H-pyrazol-4-ylamine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred mixture of 1-Methyl-5-phenoxy-1H-pyrazole-4-carboxylic acid (16.0 g; 73.3 mmol), t-BuOH (51.2 g; 691 mmol) in 1,4-dioxane under argon are added DIPEA (37.4 g; 290 mmol) and diphenylphosphoryl azide (41.6 g; 151 mmol). After 10 minutes at ambient temperature it is heated up to 110° C. and stirred for 3 hours. The solvent is evaporated and the crude material purified by column chromatography. This compound is dissolved in DCM and treated with 4 M HCl in 1,4-dioxane. It is stirred for 2 days at ambient temperature. The solvent is evaporated and the residue dissolved in water and washed with EtOAc. The aqueous layer is basified with aqueous NaHCO3 solution and is extracted with EtOAc. The organic layer is dried and concentrated to dryness.

Workup

  1. customThe solvent is evaporated
  2. customthe crude material purified by column chromatography
  3. dissolutionThis compound is dissolved in DCM
  4. additiontreated with 4 M HCl in 1,4-dioxane
  5. stirringIt is stirred for 2 days at ambient temperature
  6. customThe solvent is evaporated
  7. dissolutionthe residue dissolved in water
  8. washwashed with EtOAc
  9. extractionis extracted with EtOAc
  10. customThe organic layer is dried
  11. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-d0e2c83485044ceca1b6bec44f2d81ab
Source dataset
uspto-grants-2016_02
Patent number
US09266891B2

Reaction notes

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