Hexane → HCID 19366009, compound

HRID 850095Notes

Reaction equation

HRID 850095 reaction equation
[CH2:1]([O:3][CH2:4][N:5]1[CH:9]=[N:8][CH:7]=[N:6]1)[CH3:2].C([Li])CCC.CCCCCC.[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C:29]([OH:45])([C:36]([C:38]1[CH:43]=[CH:42][C:41](I)=[CH:40][CH:39]=1)=[CH2:37])[CH2:30][N:31]1[CH:35]=[N:34][CH:33]=[N:32]1.[Na+].[Na+].C(N(CC(O)=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C:29]([OH:45])([C:36]([C:38]1[CH:43]=[CH:42][C:41]([C:9]2[N:5]([CH2:4][O:3][CH2:1][CH3:2])[N:6]=[CH:7][N:8]=2)=[CH:40][CH:39]=1)=[CH2:37])[CH2:30][N:31]1[CH:35]=[N:34][CH:33]=[N:32]1

Participants

10

Reactant 6

HCID 8058HexaneHCID 10340Sodium CarbonateHCID 3823094HCID 3823094, compoundHCID 13020083Ethylenediaminetetraacetic acid disodium saltHCID 17892901HCID 17892901, compoundHCID 178418339Butyllithium

Product 1

HCID 19366009HCID 19366009, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-ethoxymethyl-1,2,4-triazole (0.79 g, 6.2 mmol-see Preparation 27) in tetrahydrofuran (THF) (8 ml) was stirred under a nitrogen atmosphere at -70° C. before treatment with a solution of n-butyllithium in hexane (2.5M, 2.5 ml, 6.2 mmol) The mixture was stirred for 0.25 hours and treated with a solution of anhydrous zinc chloride (1.2 g, 9.3 mmol) in THF (8 ml), then was allowed to warm to room temperature. To this mixture was added tetrakis(triphenylphosphine)palladium (0) (0.06 g, 0.06 mmol) and 2-(2,4-difluorophenyl)-3-(4-iodophenyl)-1-(1,2,4-triazol-1-yl)-3-buten-2-ol (0.7 g, 1.5 mmol-see Preparation 20) and the mixture was heated under reflux for 4 hours. After being cooled, a suspension of ethylenediaminetetraacetic acid disodium salt (10 g, 27 mmol) was added, the mixture was adjusted to pH8 with saturated sodium carbonate solution and extracted with dichloromethane (2×100 ml). The combined extracts were dried (MgSO4) and evaporated under reduced pressure. The residue was chromatographed on silica by gradient elution with dichloromethanelmethanol (98:2, 97:3, 95:5). Fractions containing the desired product were combined, evaporated under reduced pressure and the residue was triturated with ether to afford the title compound (0.55 g, 78%) as a colourless solid, m.p. 160-162° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 hours
  3. temperatureAfter being cooled
  4. additionwas added
  5. extractionextracted with dichloromethane (2×100 ml)
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. customevaporated under reduced pressure
  8. customThe residue was chromatographed on silica by gradient elution with dichloromethanelmethanol (98:2, 97:3, 95:5)
  9. additionFractions containing the desired product
  10. customevaporated under reduced pressure
  11. customthe residue was triturated with ether

Sources & evidence

ORD record
ord-add1f348b890448483ac851a5720fc76
Source dataset
uspto-grants-2000_01
Patent number
US06015825

Reaction notes

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