Trifluoroacetic acid → 2,6-Diisopropyl-N-((6-(2-((phenylamino)methyl)phenyl)pyridin-2-yl)methyl)aniline

HRID 1944836Notes

Reaction equation

HRID 1944836 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1/[N:13]=[CH:14]/[C:15]1[N:20]=[C:19]([C:21]2[CH:41]=[CH:40][CH:39]=[CH:38][C:22]=2[CH2:23][N:24]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)C(=O)OC(C)(C)C)[CH:18]=[CH:17][CH:16]=1)([CH3:3])[CH3:2].[BH3-]C#N.[Na+].FC(F)(F)C(O)=O.[OH-].[Na+]>C(O)=O.CO>[CH:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5]=1[NH:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]([C:21]2[CH:41]=[CH:40][CH:39]=[CH:38][C:22]=2[CH2:23][NH:24][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:20]=1)([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydride2×HCID 178439041HCID 178439041, compound

Product 1

HCID 667954692,6-Diisopropyl-N-((6-(2-((phenylamino)methyl)phenyl)pyridin-2-yl)methyl)aniline

Reagents, catalysts & solvents 2

HCID 284Formic AcidCatalystHCID 887MethanolSolvent

Procedure

Methanol (40 mL) and (E)-tert-butyl 2-(6-((2,6-diisopropylphenylimino)methyl)pyridin-2-yl)benzyl(phenyl)carbamate (12) (2.56 g (4.67 mmol) were combined to form a yellow suspension. Then some NaBH3CN (0.293 g, 4.66 mmol) was added followed by four drops of 88% formic acid. Then additional NaBH3CN (0.878 g, 14.0 mmol) was added in small portions over 5 minutes. The mixture was heated to reflux for 3 hours then evaporated to near dryness. Water (20 mL) and Et2O (40 mL) were then added followed by a CH2Cl2 (6 mL). The organics were separated, dried over brine then magnesium sulfate, filtered, and evaporated to a thick oil. Chloroform (25 mL) was then added to form a solution. Trifluoroacetic acid (10 mL) was added and the mixture was heated to reflux to cause gas evolution. After 45 minutes the mixture was cooled to ambient temperature and 3 M NaOH (60 mL) was added. The biphasic mixture was rapidly stirred for several minutes. The organics were separated, washed with water (50 mL) and brine (5 mL). The organics were then separated and dried over magnesium sulfate. Filtration and evaporation afforded the product as a thick oil that was dried thoroughly under reduced pressure at 65° C. Yield: 2.0 g, 95%). 1H NMR (CD2Cl2, 500 MHz): 7.77 (t, 1H), 7.39-7.58 (m, 5H), 7.31 (d, 1H), 7.02-7.12 (m, 5H), 6.63 (t, 1H), 6.58 (d, 2H), 4.62 (br, 1H), 4.41 (br, 2H), 4.23 (br, 1H), 3.97 (br, 1H), 3.35 (sept, 2H), 1.20 (d, 12H).

Workup

  1. customto form a yellow suspension
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 3 hours
  4. customthen evaporated
  5. additionWater (20 mL) and Et2O (40 mL) were then added
  6. customThe organics were separated
  7. dry with materialdried over brine
  8. filtrationmagnesium sulfate, filtered
  9. customevaporated to a thick oil
  10. additionChloroform (25 mL) was then added
  11. customto form a solution
  12. temperaturethe mixture was heated
  13. temperatureto reflux
  14. customThe organics were separated
  15. washwashed with water (50 mL) and brine (5 mL)
  16. customThe organics were then separated
  17. dry with materialdried over magnesium sulfate
  18. filtrationFiltration and evaporation

Sources & evidence

ORD record
ord-6e6a7955bb0e47afa71850110583d443
Source dataset
uspto-grants-2013_03
Patent number
US08394902B2

Reaction notes

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