2,2,2-Trifluoroethanol → N-(3-(3-(4-((2,2,2-Trifluoroethoxy)methyl)phenyl)-4,5-dihydro-5-oxo-1,2,4-triazol-1-yl)-4-chlorobenzyl)pivalamide

HRID 509055

Reaction equation

HRID 509055 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].[H-].[Na+].Br[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[NH:21][C:20](=[O:22])[N:19]([C:23]3[CH:24]=[C:25]([CH:34]=[CH:35][C:36]=3[Cl:37])[CH2:26][NH:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])[N:18]=2)=[CH:13][CH:12]=1>C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[F:1][C:2]([F:6])([F:5])[CH2:3][O:4][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[NH:21][C:20](=[O:22])[N:19]([C:23]3[CH:24]=[C:25]([CH:34]=[CH:35][C:36]=3[Cl:37])[CH2:26][NH:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:30])[CH3:31])[N:18]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 136644856N-(3-(3-(4-(bromomethyl)phenyl)-4,5-dihydro-5-oxo-1,2,4-triazol-1-yl)-4-chlorobenzyl)pivalamide

Product 1

HCID 136492414N-(3-(3-(4-((2,2,2-Trifluoroethoxy)methyl)phenyl)-4,5-dihydro-5-oxo-1,2,4-triazol-1-yl)-4-chlorobenzyl)pivalamideYield 294.5%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2,2,2-trifloro ethanol (0.042 g, 0.410 mmol) in THF was added NaH (0.017 g, 0.041 mmol) at 10° C. and continued stirring at RT for 1 h. Then solution of N-(3-(3-(4-(bromomethyl)phenyl)-4,5-dihydro-5-oxo-1,2,4-triazol-1-yl)-4-chlorobenzyl)pivalamide (Intermediate-103, 0.100 g, 0.041 mmol) in THF and TBAI (0.004 g, 0.0012 mmol) were added to the reaction mixture. The reaction mass was refluxed for 2-3 h. The reaction mass was quenched in ice and pH adjusted to 6-7 and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated to afford 0.060 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 1.12 (s, 9H), 4.11-4.17 (m, 2H), 4.28 (d, J=5.4 Hz, 2H), 4.71 (s, 2H), 7.28 (d, J=9.0 Hz, 1H), 7.41 (s, 1H), 7.46 (d, J=7.8 Hz, 2H), 7.57 (d, J=8.1 Hz, 1H), 7.85 (d, J=8.1 Hz, 2H), 8.18 (t, 1H); MS (m/z): 497.31 (M+H)+.

Workup

  1. temperatureThe reaction mass was refluxed for 2-3 h
  2. customThe reaction mass was quenched in ice
  3. extractionextracted with DCM
  4. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-48b4e28e995d4f0e96bb30d1f90976f3
Source dataset
uspto-grants-2015_08
Patent number
US09096545B2

Linked notes

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