Diethyl Ether → (s)-1-[3-(3,4-Difluoro-phenylamino)-5-(2,6-dimethyl-pyridin-4-yl)-[1,2,4]triazol-1-yl]-butan-2-ol

HRID 2092225Notes

Reaction equation

HRID 2092225 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:12]([CH2:13][C@@H:14]([OH:17])[CH2:15][CH3:16])[N:11]=[C:10]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([F:26])[CH:20]=3)[N:9]=2)[CH:5]=[C:4]([CH3:27])[N:3]=1.[CH3:28]N1C(=O)CCC1.C[Mg+].[Br-].CCOCC>C1COCC1.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Fe+3]>[F:26][C:21]1[CH:20]=[C:19]([NH:18][C:10]2[N:9]=[C:8]([C:6]3[CH:5]=[C:4]([CH3:27])[N:3]=[C:2]([CH3:28])[CH:7]=3)[N:12]([CH2:13][C@@H:14]([OH:17])[CH2:15][CH3:16])[N:11]=2)[CH:24]=[CH:23][C:22]=1[F:25]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 13387N-methyl-2-pyrrolidoneHCID 86644737(S)-1-[5-(2-Chloro-6-methyl-pyridin-4-yl)-3-(3,4-difluoro-phenylamino)-[1,2,4]triazol-1-yl]-butan-2-olHCID 178418689HCID 178418689, compound

Product 1

HCID 68486428(s)-1-[3-(3,4-Difluoro-phenylamino)-5-(2,6-dimethyl-pyridin-4-yl)-[1,2,4]triazol-1-yl]-butan-2-ol

Reagents, catalysts & solvents 2

HCID 5483663Ferric acetylacetonateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Intermediate D4 (1.1 g, 2.80 mmol) was dissolved in THF (15 ml) and iron(III) acetylacetonate (0.099 g, 0.28 mmol) and NMP (1 ml) were added. The reaction mixture was then cooled to 0° C. Under N2 (gas) protection, CH3MgBr 3M in Et2O (4 ml, 12 mmol) was added slowly. The reaction mixture was warmed to room temperature and stirred for one hour until the reaction was finished. The reaction mixture was then quenched with saturated NH4Cl solution and then extracted by CH2Cl2 (3×30 ml). The combined organic phase was washed by brine, dried over MgSO4, filtered and the solvent was evaporated in vacuo. The residue was purified by reversed-phase high-performance liquid chromatography (Shandon Hyperprep® C18 BDS (Base Deactivated Silica) 8 μm, 250 g, I.D. 5 cm). A gradient with 2 or 3 mobile phases was applied (phase A: a 0.25% NH4HCO3 solution in water; phase B: CH3OH (optional); phase C: CH3CN).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. customThe reaction mixture was then quenched with saturated NH4Cl solution
  3. extractionextracted by CH2Cl2 (3×30 ml)
  4. washThe combined organic phase was washed by brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent was evaporated in vacuo
  8. customThe residue was purified by reversed-phase high-performance liquid chromatography (Shandon Hyperprep® C18 BDS (Base Deactivated Silica) 8 μm, 250 g, I.D. 5 cm)

Sources & evidence

ORD record
ord-116e30e8040847b1b78f94fcda520bf7
Source dataset
uspto-grants-2013_05
Patent number
US08440701B2

Reaction notes

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