Potassium Hydroxide → 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-ol

HRID 1800316Notes

Reaction equation

HRID 1800316 reaction equation
Br[C:2]1[CH:23]=[CH:22][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:19]([CH3:21])[CH3:20])[N:16]=[CH:17][N:18]=1)[N:7]=3.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[OH-:54].[K+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:19]([N:15]1[C:14]([C:8]2[N:7]=[C:6]3[C:5]4[CH:22]=[CH:23][C:2]([OH:54])=[CH:3][C:4]=4[O:13][CH2:12][CH2:11][N:10]3[CH:9]=2)=[N:18][CH:17]=[N:16]1)([CH3:21])[CH3:20]

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 1360309202-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-olYield 46%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Alternatively, 8-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (9.5 g, 25.4 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (855 mg, 2.0 mmol), tris(dibenzylideneacetone)dipalladium (0) (475 mg, 0.5 mmol) and potassium hydroxide (4.2 g, 76.2 mmol) were suspended in dioxane (29 mL) and water (15 mL). The suspension was degassed with nitrogen and the reaction mixture heated at 90° C. for 1 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (20 mL). The aqueous fraction was acidified to pH˜5 by addition of hydrochloric acid (1M) causing a precipitate to form. The suspension was extracted with ethyl acetate (3×15 mL). The combined organic extracts were dried (MgSO4), concentrated in vacuo. The resultant residue was triturated with diethyl ether to yield 490 as an orange solid (3.6 g, 46%). 1H NMR (400 MHz, DMSO-d6) δ 9.90 (1H, br s), 8.22 (1H, d, J=8.9 Hz), 7.88 (1H, s), 7.82 (1H, s), 6.61 (1H, dd, J=8.9, 2.6 Hz), 6.41 (1H, d, J=2.6 Hz), 5.90 (1H, sept, J=6.5 Hz), 4.49-4.39 (4H, m), 1.47 (6H, d, J=6.5 Hz)

Workup

  1. customThe suspension was degassed with nitrogen
  2. additionThe reaction mixture was diluted with water (50 mL)
  3. extractionextracted with ethyl acetate (20 mL)
  4. additionThe aqueous fraction was acidified to pH˜5 by addition of hydrochloric acid (1M)
  5. customto form
  6. extractionThe suspension was extracted with ethyl acetate (3×15 mL)
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe resultant residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-03ffd490c2d14732b7638af024d5df83
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

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