Hexane → HCID 20186855, compound

HRID 2309115Notes

Reaction equation

HRID 2309115 reaction equation
[Cl:1][C:2]1[CH:42]=[CH:41][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][O:16][C:17]3[CH:18]=[C:19]([CH:38]=[CH:39][CH:40]=3)[O:20][C:21]3[N:25]([CH2:26][C:27]4[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=4)[N:24]=[N:23][C:22]=3[C:35]([OH:37])=O)[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[Cl-].[Cl-].C([Al+2])C.CCCCCC>ClCCl.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][O:16][C:17]3[CH:40]=[CH:39][C:38]4[C:35](=[O:37])[C:22]5[N:23]=[N:24][N:25]([CH2:26][C:27]6[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=6)[C:21]=5[O:20][C:19]=4[CH:18]=3)[CH2:9][CH2:8]2)=[CH:41][CH:42]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 65578Oxalyl chlorideHCID 16686341Ethyl aluminium dichlorideHCID 20186857HCID 20186857, compound

Product 1

HCID 20186855HCID 20186855, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

5-{3-{3-[4-(4-Chlorobenzyl)-1-piperazinyl]-propoxy}phenoxy}-1-(4-methoxybenzyl)-1,2,3-triazole-4-carboxylic acid, (0.50 g, 0.84 mmole), was dissolved in dry dichloromethane (20 ml) and oxalyl chloride, (1.00 ml, 11.7 mmole), added, followed by 1 drop of dimethylformamide. The reaction was stirred overnight, then excess oxalyl chloride and solvent evaporated in vacuo. The acid chloride was resuspended in dry dichloromethane, (20 ml), under nitrogen and cooled with stirring in an ice bath. A 25% solution of ethyl aluminium dichloride in hexane, (1.61 ml, 3.38 mmole) was added dropwise and the reaction stirred in ice for 2 hours, warmed to room temperature over 1 hour, and stirred for a further 3 hours. The mixture was quenched with dilute hydrochloric acid, (50 ml) and left to stand overnight. The resultant cream solid was filtered, stirred in water, (25 ml), and neutralized to pH7 with dilute sodium hydrogen carbonate solution. The aqueous phase was decanted and the gummy residue purified by column chromatography using silica gel, eluting with chloroform to give the title compound as a colourless oil which crystallized on trituration with methanol. 171 mg (35%) mp (MeOH) 135°-138° C. νmax (mull) 1518, 1535, 1565, 1620, 1680 cm-1 δ(CDCl3) 2.00 (2H, m, CH2), 2.50 (10H, bs, piperazinyl+CH2), 3.43 (2H, s, N--CH2), 3.77 (3H, s, OCH3), 4.13 (2H, t, J 6 Hz, OCH2), 5.56 (2H, s, N--CH2), 6.93 (2H, m, aromatics), 7.12 (4H, ABq, Δν 45 Hz, J 9 Hz, C6H4OCH3), 7.29 (4H, s, C6H4Cl) 8.28 (1H, d, J 9 Hz, aromatic).

Workup

  1. customexcess oxalyl chloride and solvent evaporated in vacuo
  2. temperaturecooled
  3. stirringwith stirring in an ice bath
  4. stirringthe reaction stirred in ice for 2 hours
  5. stirringstirred for a further 3 hours
  6. customThe mixture was quenched with dilute hydrochloric acid, (50 ml)
  7. waitleft
  8. waitto stand overnight
  9. filtrationThe resultant cream solid was filtered
  10. stirringstirred in water, (25 ml)
  11. customThe aqueous phase was decanted
  12. customthe gummy residue purified by column chromatography
  13. washeluting with chloroform

Sources & evidence

ORD record
ord-eada405adccb48ccbce1f5b8ecb7fcd8
Source dataset
uspto-grants-1987_09
Patent number
US04692526

Reaction notes

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