tert-Butanol → 1-[5-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-thienyl]-2,2,2-trifluoroethanone

HRID 1715351Notes

Reaction equation

HRID 1715351 reaction equation
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([C:11]1[S:15][C:14]([C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1)#[CH:10].[N-:22]=[N+:23]=[N-:24].[Na+].CC(O)(C)C>O.[O-]S([O-])(=O)=O.[Cu+2]>[CH2:1]([N:22]1[CH:10]=[C:9]([C:11]2[S:15][C:14]([C:16](=[O:21])[C:17]([F:19])([F:18])[F:20])=[CH:13][CH:12]=2)[N:24]=[N:23]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 7498Benzyl BromideHCID 33557Sodium AzideHCID 576201031-(5-Ethynyl-2-thienyl)-2,2,2-trifluoroethanone

Product 1

HCID 177473381-[5-(1-Benzyl-1H-1,2,3-triazol-4-yl)-2-thienyl]-2,2,2-trifluoroethanone

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

Benzyl bromide (1.0 eq), D2 (1.05 eq) and NaN3 (1.05 eq) were suspended in a 1:1 mixture of H2O and t-BuOH (0.1M) in a 10-mL glass vial equipped with a small magnetic stirring bar. To this was added Cu powder (0.8 eq) and CuSO4 solution (1.0M, 0.2 eq) and the vial was tightly sealed with an aluminum/Teflon crimp top. The mixture was then irradiated for 10 min at 125° C., using an irradiation power of 100 W. After completion of the reaction, the vial was cooled to 50° C. with air jet cooling before it was opened. It was then diluted with H2O and precipitated product was collected by filtration, and washed with cold H2O, followed by 0.25M HCl and finally with Petroleum ether to furnish a crude material which was purified by preparative RP-HPLC, using H2O (+0.1% TFA) and MeCN (+0.1% TFA) as eluents (column: C18) and the desired fractions were freeze dried to yield the product (D3). 1H NMR (400 MHz, DMSO, 300). δ 8.92 (1H, s), 8.16-8.12 (1H, m), 7.73 (1H, d, J=4.4 Hz), 7.44-7.33 (5H, m), 5.70 (2H, s). MS (ES) C15H10F3N3OS requires: 337, found: 338 (M+H+) and 356 (M+H2O+H)+.

Workup

  1. customequipped with a small magnetic stirring bar
  2. customThe mixture was then irradiated for 10 min at 125° C.
  3. customAfter completion of the reaction
  4. temperaturecooling before it
  5. customprecipitated product
  6. filtrationwas collected by filtration
  7. washwashed with cold H2O
  8. customto furnish a crude material which
  9. customwas purified by preparative RP-HPLC
  10. customdried

Sources & evidence

ORD record
ord-74fea647c546486ea0dd7c47fee74afe
Source dataset
uspto-grants-2010_09
Patent number
US07799825B2

Reaction notes

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