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

HRID 928628Notes

Reaction equation

HRID 928628 reaction equation
BrC1N=C(C=O)C=CC=1.C(C1C=CC=C(C(C)C)C=1N)(C)C.[Br:23][C:24]1[N:29]=[C:28](/[CH:30]=[N:31]/[C:32]2[C:37]([CH:38]([CH3:40])[CH3:39])=[CH:36][CH:35]=[CH:34][C:33]=2[CH:41]([CH3:43])[CH3:42])[CH:27]=[CH:26][CH:25]=1.[BH3-]C#N.[Na+]>C(O)C.O.CO.C(O)(=O)C>[Br:23][C:24]1[N:29]=[C:28]([CH2:30][NH:31][C:32]2[C:37]([CH:38]([CH3:39])[CH3:40])=[CH:36][CH:35]=[CH:34][C:33]=2[CH:41]([CH3:43])[CH3:42])[CH:27]=[CH:26][CH:25]=1

Participants

9

Reactant 4

HCID 32484DiisopropylanilineHCID 27570096-Bromopyridine-2-carbaldehydeHCID 5003444Sodium cyanoborohydrideHCID 178439040HCID 178439040, compound

Product 1

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

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of 85.0 g (457 mmol) of 6-bromopyridine-2-carbaldehyde and 80.9 g (457 mmol) of 2,6-diisopropylaniline in 1000 ml of ethanol was refluxed for 8 h. The obtained solution was evaporated to dryness, and the residue was re-crystallized from 200 ml of methanol. In argon atmosphere, to thus obtained 113.5 g (329 mmol) of N-[(1E)-(6-bromopyridin-2-yl)methylene]-2,6-diisopropylaniline were added 33.16 g (526 mmol) of NaBH3CN, 9 ml of acetic acid and 1000 ml of methanol. This mixture was refluxed for 12 h, then cooled to room temperature, poured into 1000 ml of water, and crude product was extracted with 3×200 ml of ethyl acetate. The combined extract was dried over sodium sulfate and evaporated to dryness. The residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate=10:1, vol.). Yield 104.4 g (66%) of a yellow oil. Anal. calc. for C18H23BrN2: C, 62.25; H, 6.68; N, 8.07. Found: C, 62.40; H, 6.87; N, 7.90. 1H NMR (CDCl3): δ 7.50 (m, 1H, 4-H in Py), 7.38 (m, 1H, 5-H in Py), 7.29 (m, 1H, 3-H in Py), 7.05-7.12 (m, 3H, 3,4,5-H in 2,6-iPr2C6H3), 4.18 (s, 2H, CH2NH), 3.94 (br.s, 1H, NH), 3.33 (sept, J=6.8 Hz, 2H, CHMe2), 1.23 (d, J=6.8 Hz, 12H, CHMe2).

Workup

  1. customThe obtained solution was evaporated to dryness
  2. customthe residue was re-crystallized from 200 ml of methanol
  3. temperatureThis mixture was refluxed for 12 h
  4. extractionwas extracted with 3×200 ml of ethyl acetate
  5. extractionThe combined extract
  6. dry with materialwas dried over sodium sulfate
  7. customevaporated to dryness
  8. customThe residue was purified by flash chromatography on silica gel 60 (40-63 um, eluent: hexane-ethyl acetate=10:1, vol.)

Sources & evidence

ORD record
ord-3837ce07e35f4c93a451e37dbdf70611
Source dataset
uspto-grants-2016_03
Patent number
US09290519B2

Reaction notes

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