2-Trityl-5-methyl tetrazole → N-(2,4-dimethylphenyl)-4-(1-hydroxy-3-(2-trityl-2H-tetrazol-5-yl)propyl)-N-isobutylbenzenesulfonamide

HRID 1746434Notes

Reaction equation

HRID 1746434 reaction equation
[CH3:1][C:2]1[N:3]=[N:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:6]=1.[Li]CCCC.[CH3:31][C:32]1[CH:37]=[C:36]([CH3:38])[CH:35]=[CH:34][C:33]=1[N:39]([CH2:52][CH:53]([CH3:55])[CH3:54])[S:40]([C:43]1[CH:48]=[CH:47][C:46]([CH:49]2[CH2:51][O:50]2)=[CH:45][CH:44]=1)(=[O:42])=[O:41]>O1CCCC1>[CH3:31][C:32]1[CH:37]=[C:36]([CH3:38])[CH:35]=[CH:34][C:33]=1[N:39]([CH2:52][CH:53]([CH3:55])[CH3:54])[S:40]([C:43]1[CH:48]=[CH:47][C:46]([CH:49]([OH:50])[CH2:51][CH2:1][C:2]2[N:3]=[N:4][N:5]([C:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:6]=2)=[CH:45][CH:44]=1)(=[O:42])=[O:41]

Participants

5

Reactant 3

HCID 109583602-Trityl-5-methyl tetrazoleHCID 86731600N-(2,4-dimethylphenyl)-N-isobutyl-4-(oxiran-2-yl)benzenesulfonamideHCID 178418339Butyllithium2×

Product 1

HCID 86731599N-(2,4-dimethylphenyl)-4-(1-hydroxy-3-(2-trityl-2H-tetrazol-5-yl)propyl)-N-isobutylbenzenesulfonamideYield 13.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-methyl-2-trityl-2H-tetrazole (68.5 mg, 0.21 mmol) in tetrahydrofuran (THF) (1 mL), stirred under nitrogen at −70° C., was added a solution of n-BuLi (1.6 M in hexanes, 0.144 mL, 0.231 mmol) in Tetrahydrofuran (THF) (1 mL) dropwise over 1 minute. The reaction mixture was then stirred at −78° C. for 45 minutes. N-(2,4-dimethylphenyl)-N-isobutyl-4-(oxiran-2-yl)benzenesulfonamide (108 mg, 0.300 mmol) in Tetrahydrofuran (THF) (1 mL) was added dropwise at −78° C. over 1 minute. The reaction mixture was then stirred at −78° C. for a further 1 hour and then allowed to warm to room temperature. The reaction was carefully quenched using a few drops of water, under nitrogen. Ethyl acetae (3 mL) and water (2 mL) were added and the reaction stirred vigorously for 5 minutes. The organic phase was separated using a hydrophilic frit and concentrated in vacuo to give a residue. LCMS analysis showed incomplete reaction, so the above reaction procedure repeated using fresh n-butyl lithium solution and reintroducing the crude residue instead of new starting material, this resulted in improved conversion. The residue was then purified by flash (Si) chromatography (using a 0-25% ethyl acetate-cyclohexane gradient) to give the required product (20 mg) as a colourless gum. LCMS RT 1.56 mins.

Workup

  1. stirringThe reaction mixture was then stirred at −78° C. for a further 1 hour
  2. temperatureto warm to room temperature
  3. customThe reaction was carefully quenched
  4. additionEthyl acetae (3 mL) and water (2 mL) were added
  5. stirringthe reaction stirred vigorously for 5 minutes
  6. customThe organic phase was separated
  7. concentrationconcentrated in vacuo
  8. customto give a residue
  9. customreaction
  10. customso the above reaction procedure
  11. customthis resulted in improved conversion
  12. customThe residue was then purified by flash (Si) chromatography (

Sources & evidence

ORD record
ord-95dce8fa2c584cb49ce3698bb7e5c25d
Source dataset
uspto-grants-2015_10
Patent number
US09150508B2

Reaction notes

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