Acetic Acid → N-[(6-Bromopyridin-2-yl)methyl]-2,6-diisopropylaniline

HRID 513910Notes

Reaction equation

HRID 513910 reaction equation
[Br:1][C:2]1[N:7]=[C:6](/[CH:8]=[N:9]/[C:10]2[C:15]([CH:16]([CH3:18])[CH3:17])=[CH:14][CH:13]=[CH:12][C:11]=2[CH:19]([CH3:21])[CH3:20])[CH:5]=[CH:4][CH:3]=1.[BH3-]C#N.[Na+].CC(O)=O.CO>O>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][NH:9][C:10]2[C:15]([CH:16]([CH3:17])[CH3:18])=[CH:14][CH:13]=[CH:12][C:11]=2[CH:19]([CH3:21])[CH3:20])[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 178439040HCID 178439040, compound

Product 1

HCID 90311811N-[(6-Bromopyridin-2-yl)methyl]-2,6-diisopropylaniline

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 25.0 g (134 mmol) of 6-bromopyridine-2-carbaldehyde, 23.8 g (134 mmol) of 2,6-diisopropylaniline and 1.15 g (6.70 mmol) of TsOH in 600 ml of toluene was refluxed for 15 min using a Soxhlet apparatus filled with CaCl2. The obtained solution was evaporated to dryness, and the residue was re-crystallized from 100 ml of methanol to give the imine product N-[(1E)-(6-bromopyridin-2-yl)methylene]-2,6-diisopropylaniline as a yellow crystalline solid (23.9 g). In argon atmosphere, a mixture of 22.4 g (65.0 mmol) of N-[(1E)-(6-bromopyridin-2-yl)methylene]-2,6-diisopropylaniline, 6.53 g (104 mmol) of NaBH3CN, 2 ml of AcOH and 430 ml of methanol was refluxed for 12 h. The obtained mixture was cooled, poured into 1000 ml of water, and then extracted with 3×200 ml of ethyl acetate. The combined extract was dried over MgSO4 and evaporated to dryness. The residue was purified by flash chromatography on silica gel 60 (40-63 μm, eluent: hexane-ethyl acetate=10:1, vol.). Yield 19.8 g (43%) of a yellow oil. Anal. calc. for C18H23BrN2: C, 62.25; H, 6.68; N, 8.07. Found: C, 62.40; H, 6.77; N, 7.96. 1H NMR (CDCl3): δ 7.50 (m, 1H, 4-H in 6-bromopyridyl), 7.38 (m, 1H, 5-H in 6-bromopyridyl), 7.28 (m, 1H, 3-H in 6-bromopyridyl), 7.01-7.11 (m, 3H, 3,4,5-H in 2,6-diisopropylphenyl), 4.16 (s, 2H, CH2N), 3.93 (br.s, 1H, NH), 3.31 (sep, J=6.9 Hz, 2H, CHMe2), 1.22 (d, J=6.9 Hz, 12H, CHMe2).

Workup

  1. temperaturewas refluxed for 12 h
  2. temperatureThe obtained mixture was cooled
  3. extractionextracted with 3×200 ml of ethyl acetate
  4. extractionThe combined extract
  5. dry with materialwas dried over MgSO4
  6. customevaporated to dryness
  7. customThe residue was purified by flash chromatography on silica gel 60 (40-63 μm, eluent: hexane-ethyl acetate=10:1, vol.)

Sources & evidence

ORD record
ord-d0e494867df2447694bd499f00b603ed
Source dataset
uspto-grants-2015_08
Patent number
US09102773B2

Reaction notes

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