Triethylamine → (+/-)-N-[2,6-Bis(1-methylethyl)phenyl]-2-dodecyl-alpha-fluoro-alpha-phenyl-2H-tetrazole-5-acetamide

HRID 264064Notes

Reaction equation

HRID 264064 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([N:19]1[N:23]=[N:22][C:21]([C:24]([F:34])([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:25]([OH:27])=O)=[N:20]1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH:35]([C:38]1[CH:44]=[CH:43][CH:42]=[C:41]([CH:45]([CH3:47])[CH3:46])[C:39]=1[NH2:40])([CH3:37])[CH3:36].CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[CH3:47][CH:45]([C:41]1[CH:42]=[CH:43][CH:44]=[C:38]([CH:35]([CH3:37])[CH3:36])[C:39]=1[NH:40][C:25](=[O:27])[C:24]([F:34])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:21]1[N:22]=[N:23][N:19]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[N:20]=1)[CH3:46]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 32484DiisopropylanilineHCID 65578Oxalyl chlorideHCID 539372962-Dodecyl-alpha-fluoro-alpha-phenyl-2H-tetrazole-5-acetic acid

Product 1

HCID 9807593(+/-)-N-[2,6-Bis(1-methylethyl)phenyl]-2-dodecyl-alpha-fluoro-alpha-phenyl-2H-tetrazole-5-acetamideYield 44.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (0.08 mL, 0.92 mole) was added to a stirred solution of 2-dodecyl-α-fluoro-α-phenyl-2H-tetrazole-5-acetic acid (0.24 g, 0.61 mmole) in 5 mL of CH2Cl2 at room temperature. The mixture was stirred 60 minutes, the one drop of DMF was added (immediate gas evolution). The solution was stirred overnight, concentrated (rotovap), toluene was added, and the solution concentrated again. The residue was dissolved in CH2Cl2 (3 mL) and added to a stirred solution of 2,6-diisopropylaniline (0.12 mL, 0.61 mmole) and Et3N (0.14 mL, 1.0 mole) in CH2Cl2 (2 mL) cooled to 0° C. under dry nitrogen. After 20 minutes, the ice bath was removed and the solution allowed to warm to room temperature and stirred for 3 days. The mixture was then diluted with ethyl acetate (150 mL) and washed with dilute HCl (50 mL), bicarbonate (50 mL), brine (50 mL), and dried. Filtration and concentration afforded an oil which was flash chromatographed (silica gel, 10:1 hexanes-ethyl acetate) to produce 150 mg of the title compound as an oil which solidified on standing.

Workup

  1. stirringThe solution was stirred overnight
  2. concentrationconcentrated (rotovap), toluene
  3. additionwas added
  4. concentrationthe solution concentrated again
  5. dissolutionThe residue was dissolved in CH2Cl2 (3 mL)
  6. waitAfter 20 minutes
  7. customthe ice bath was removed
  8. temperatureto warm to room temperature
  9. stirringstirred for 3 days
  10. additionThe mixture was then diluted with ethyl acetate (150 mL)
  11. washwashed with dilute HCl (50 mL), bicarbonate (50 mL), brine (50 mL)
  12. customdried
  13. filtrationFiltration and concentration
  14. customafforded an oil which
  15. customchromatographed (silica gel, 10:1 hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-5d0095a3b0aa48519a96fcc0c54b5e30
Source dataset
uspto-grants-1997_07
Patent number
US05646170

Reaction notes

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