Tetrabutylammonium Fluoride → 2-(4-tert-Butylphenyl)-N-[(3,4-difluorophenyl)(1-methyl-1H-1,2,3-triazol-4-yl)methyl]acetamide

HRID 877380Notes

Reaction equation

HRID 877380 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([NH:14][CH:15]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=2)[C:16]2[N:17]=[N:18][N:19]([CH2:21][Si](C)(C)C)[CH:20]=2)=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([NH:14][CH:15]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=2)[C:16]2[N:17]=[N:18][N:19]([CH3:21])[CH:20]=2)=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 671758872-(4-tert-Butylphenyl)-N-((3,4-difluorophenyl){1-[(trimethylsilyl)methyl]-1H-1,2,3-triazol-4-yl}methyl)acetamide

Product 1

HCID 529321562-(4-tert-Butylphenyl)-N-[(3,4-difluorophenyl)(1-methyl-1H-1,2,3-triazol-4-yl)methyl]acetamideYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a 10 ml round bottom flask containing a solution of 2-(4-tert-butylphenyl)-N-((3,4-difluorophenyl){1-[(trimethylsilyl)methyl]-1H-1,2,3-triazol-4-yl}-methyl)acetamide (0.062 mg, 0.132 mmol) in 1.0 ml of anhydrous THF at rt was added 1.0N tetrabutylammonium fluoride in THF (0.145 ml, 0.145 mmol). The resulting solution was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with CH2Cl2. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum. Purification by preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column) to afford 0.046 g (88%) of the title compound. Purification by super fluid (CO2/MeOH) chiral column yielded first enathiomer (19 mg) (36.2%), and second enathiomer (21 mg) (40%) 1H NMR (CDCl3, 400 MHz) δ 7.359 (m, 2H), 7.307 (s, 1H), 7.183 (m, 2H), 7.009 (m, 3H), 6.769 (d, J=7.32 Hz, 1H), 6.216 (d, J=7.57 Hz, 1H), 4.059 (s, 3H), 3.581 (ABq, J=15.75 Hz, 2H), 1.311 (s, 9H). ES-MS [M+1]+: 399.2.

Workup

  1. extractionextracted with CH2Cl2
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuum
  6. customPurification
  7. additionby preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column)

Sources & evidence

ORD record
ord-07d4968bdcfc460e93389038cd600f1b
Source dataset
uspto-grants-2015_03
Patent number
US08987310B2

Reaction notes

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